User login
Isatuximab Quadruplet Approval Could Change the Landscape for Treating Myeloma
The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.
The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.
Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”
Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.
So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?
“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”
Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.
However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?
“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”
She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”
“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.
Patient preference and access are also important considerations, as is cost, he noted.
Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.
“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
How Will This Combination Be Integrated Into Daily Clinical Practice?
“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.
Dr. Mohty added that the multiple myeloma story is changing and evolving.
“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.
For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.
“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”
Both the IMROZ study and the EMJ article were funded by Sanofi.
Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
A version of this article appeared on Medscape.com.
The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.
The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.
Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”
Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.
So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?
“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”
Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.
However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?
“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”
She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”
“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.
Patient preference and access are also important considerations, as is cost, he noted.
Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.
“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
How Will This Combination Be Integrated Into Daily Clinical Practice?
“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.
Dr. Mohty added that the multiple myeloma story is changing and evolving.
“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.
For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.
“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”
Both the IMROZ study and the EMJ article were funded by Sanofi.
Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
A version of this article appeared on Medscape.com.
The findings, presented on September 26 at the annual meeting of the International Myeloma Society, support the four-drug combination known as Isa-VRd as a potential new standard of care (SOC) supplanting VRd alone as the SOC in this setting, according to Meletios Dimopoulos, MD, of the University of Athens, Greece.
The IMROZ findings — the first from a phase 3 study of an anti-CD38 monoclonal antibody given in combination with VRd — were also reported in May at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in The New England Journal of Medicine.
“The significant progression-free benefit observed with Sarclisa with combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma,” first author Thierry Facon, MD, told this news organization at ASCO.
Dr. Thierry, of the University of Lille, and the French Academy of Medicine in Paris, France, added that Isa-VRd has the potential as “a first-in-class combination to address gaps in care for newly diagnosed multiple myeloma transplant-ineligible patients.”
Isatuximab in combination with VRd was subsequently approved by the US Food and Drug Administration (FDA) for this indication, as reported on September 23 by this news organization.
So, what will this quadruplet mean for the treatment of multiple myeloma? IMROZ study coauthors Meral Beksac, MD, of Istinye University, Istanbul, and Liv Hospital Ankara, Turkey, and Mohamad Mohty, MD, of Sorbonne University, Saint-Antoine Hospital, Paris, France, provided some insights in a recent interview, telling the European Medical Journal (EMJ) Hematology that Isa-VRd is a “welcome addition” to the multiple myeloma armamentarium.
Should Isa-VRd Be Considered the New First-Choice Frontline Treatment for Transplant-Ineligible Patients?
“The short answer is yes,” Dr. Mohty told EMJ. “Based on this trial, quadruplet should become the preferred regimen in the population of patients represented by these inclusion criteria.”
Dr. Beksac agreed that Isa-VRd will play a role in frontline management for transplant-ineligible patients.
However, both noted that despite having a favorable safety profile similar to VRd, Isa-VRd may not be well tolerated in elderly and frail patients. Demonstrably frail patients were excluded from IMROZ, and this is a factor that should be considered in the practice setting, they agreed.
Will Isa-VRd Change How Patients Are Evaluated for Transplant Eligibility?
“The cutoff for transplant eligibility differs from one country to another, and today, we do not have consensus around an agreed-upon age limit,” Dr. Beksac said. “We further rely on frailty and the patient’s performance status, not only at diagnosis but at later stages as well.”
She also noted that “[t]he introduction of very effective systemic regimens with similar efficacy to [hematopoietic stem cell transplant (HSCT)] has seen a shift towards non-transplant regimens, particularly in the USA.”
“In many centers in Europe, these patients [in IMROZ] would be considered transplant eligible. Hence, for this group of patients who are not too old, but not too young, and fit, IMROZ is offering a non-transplant-based treatment with similar efficacy to what can be achieved with HSCT,” Dr. Mohty added.
Patient preference and access are also important considerations, as is cost, he noted.
Younger transplant-eligible patients may prefer transplant over continuous treatment for life, whereas some might prefer long-term treatment over a stem cell protocol that will require months off of work, he and Dr. Beksac explained.
“Based on this trial, we will likely see a decline in the number of transplants,” Dr. Mohty predicted. “With the IMROZ data, we have something valid that we can offer patients without any prejudice to their outcome.”
How Will This Combination Be Integrated Into Daily Clinical Practice?
“My interpretation would be that this protocol will be conceived as an applicable protocol that can be adapted to our daily practice,” Dr. Beksac said.
Dr. Mohty added that the multiple myeloma story is changing and evolving.
“It’s not transplant versus no transplant, it’s who is going to receive quadruplet and who’s going to receive less than a quadruplet, who is fit and who is unfit,” he explained, adding that physicians will likely adapt the Isa-VRd regimen for real-world use based on clinical judgment.
For example, the quadruplet may be combined “in a kind of VRd-light version to start with, and maybe we can adapt later depending on the tolerability of the patient,” Dr. Beksac added.
“Until recently, we thought that transplant is the gold standard for everybody whenever possible. Now, we have a more nuanced answer, offering a regimen that actually is as effective, and may even be better, than transplant,” Dr. Mohty said. “So, it’s a most welcome addition to what we do.”
Both the IMROZ study and the EMJ article were funded by Sanofi.
Dr. Dimopoulos reported ties with Amgen, BeiGene, BMS, Janssen, Sanofi, and Takeda. Dr. Beksac disclosed relationships with Amgen, BMS, GSK, Janssen, Sanofi, and Takeda. Dr. Mohty reported ties with Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, GSK, Janssen-Cilag, Jazz Pharmaceuticals, and others.
A version of this article appeared on Medscape.com.
FROM IMS 2024
Extended virus shedding after COVID-19 in some patients with cancer
Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma.
The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine.
Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York.
“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.
Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.
Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said.
Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
Shedding of viable virus
For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).
Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.
There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection.
In total, 78 respiratory samples were collected.
“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”
Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.
For 11 patients, the team obtained serial sample genomes and found that “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma.
The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine.
Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York.
“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.
Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.
Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said.
Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
Shedding of viable virus
For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).
Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.
There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection.
In total, 78 respiratory samples were collected.
“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”
Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.
For 11 patients, the team obtained serial sample genomes and found that “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma.
The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine.
Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York.
“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.
Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.
Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said.
Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
Shedding of viable virus
For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).
Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.
There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection.
In total, 78 respiratory samples were collected.
“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”
Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.
For 11 patients, the team obtained serial sample genomes and found that “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patient-focused precautions, testing help blunt pandemic effects on heme-onc unit
Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.
That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.
“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.
The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.
COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.
“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”
Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”
Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.
Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.
Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”
In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.
The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.
For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.
The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections. Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.
LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.
By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.
“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”
The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.
Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.
Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.
That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.
“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.
The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.
COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.
“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”
Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”
Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.
Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.
Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”
In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.
The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.
For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.
The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections. Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.
LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.
By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.
“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”
The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.
Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.
Keeping hematologic oncology patients on their treatment regimens and caring for inpatients with hematologic malignancies remained “manageable” during the first 2 months of the COVID-19 pandemic at Levine Cancer Institute in Charlotte, N.C.
That level of manageability has partly been because a surge in cases so far hasn’t arrived at Levine or in most of the surrounding North Carolina and South Carolina communities it serves. As of May 15, 2020, the total number of confirmed and reported COVID-19 cases had reached about 19,000 in North Carolina, and just under 9,000 in South Carolina, out of a total population in the two states of close to 16 million. What’s happened instead at Levine Cancer Institute (LCI) has been a steady but low drumbeat of cases that, by mid-May 2020, totaled fewer than 10 patients with hematologic malignancies diagnosed with COVID-19.
“For a large system with multiple sites throughout North and South Carolina that saw 17,200 new patients in 2019 – including solid tumor, benign hematology, and malignant hematology patients – with 198,000 total patient visits, it is safe to say that we are off to a good start. However, we remain in the early throes of the pandemic and we will need to remain vigilant going forward,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in LCI’s Department of Hematologic Oncology and Blood Disorders.
The limited effects to date of COVID-19 at LCI has been thanks to a regimen of great caution for preventing infections that’s been consistently conveyed to LCI patients from before the pandemic’s onset, liberal testing that started early, a proactive plan to defer and temporarily replace infusion care when medically appropriate, a novel staffing approach designed to minimize and contain potential staff outbreaks, and an early pivot to virtual patient contact when feasible.
COVID-19 has had limited penetration into the LCI case load because patients have, in general, “been very careful,” said Dr. Voorhees.
“My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious even before the coronavirus using distancing, masking, and meticulous hand hygiene,” he said in an interview that reviewed the steps LCI took starting in March to confront and manage the effects of the then-nascent pandemic. “Since we started screening asymptomatic patients in the inpatient and outpatient settings we have identified only one patient with COVID-19 infection, which supports the low rate of infection in our patient population thus far.”
Another key step was the launch of “robust” testing for the COVID-19 virus starting on March 9, using an in-house assay from LCI’s parent health system, Atrium Health, that delivered results within 24 hours. Testing became available at LCI “earlier than at many other health systems.” At first, testing was limited to patients or staff presenting with symptoms, but in the following weeks, it expanded to more patients, including those without symptoms who were scheduled for treatment at the apheresis center, cell donors and cell recipients, patients arriving for inpatient chemotherapy or cellular therapy, patients arriving from a skilled nursing facility or similar environments, and more recently, outpatient chemotherapy patients. “We’re now doing a lot of screening,” Dr. Voorhees said. “In general, screening has been well received because patients recognize that it’s for their own safety.”
Another piece of COVID-19 preparedness was a move toward technology as an alternative to face-to-face encounters between patients and staff. “We adopted virtual technology early.” When medically appropriate, they provided either video consultations with more tech-savvy patients or telephone-based virtual visits for patients who preferred a more familiar interface. As LCI starts the process of reentry for patients whose face-to-face encounters were deferred, virtual visits will remain an important facet of maintaining care while limiting exposure for appropriate patients and facilitating adequate space for social distancing in the clinics and infusion centers.
Atrium Health also launched a “virtual hospital” geared to intensified remote management of COVID-19 patients who aren’t sick enough for hospitalization. “People who test positive automatically enter the virtual hospital and have regular interactions with their team of providers,” with LCI providing additional support for their patients who get infected. Patients receive an equipment kit that lets them monitor and transmit their vital signs. The virtual hospital program also helps expedite personal needs like delivery of prescriptions and food. “It helps patients manage at home, and has been incredibly useful,” said Dr. Voorhees.
Perhaps the most challenging step LCI clinicians took to preclude a potential COVID-19 case surge was to review all patients receiving infusional therapy or planned cellular therapy and triage those who could potentially tolerate a temporary change to either an oral, at-home regimen or to a brief hold on their treatment. Some patients on maintenance, outpatient infusion-therapy regimens “expressed concern about coming to the clinic. We looked at the patients scheduled to come for infusions and decided which visits were essential and which were deferrable without disrupting care by briefly using a noninfusional approach,” said Dr. Voorhees. The number of patients who had their regimens modified or held was “relatively small,” and with the recent recognition that a surge of infections has not occurred, “we’re now rolling out cautious reentry of those patients back to their originally prescribed chemotherapy.”
In addition to concerns of exposure at infusion clinics, there are concerns about the heightened susceptibility of immunosuppressed hematologic oncology patients to COVID-19 and their risk for more severe infection. “Our view is that, if patients tested positive, continuing immunosuppressive treatment would likely be detrimental,” so when possible treatment is temporarily suspended and then resumed when the infection has cleared. “When patients test positive for a prolonged period, a decision to resume treatment must be in the best interests of the patient and weigh the benefits of resuming therapy against the risks of incurring a more severe infection by restarting potentially immunosuppressive therapy,” Dr. Voorhees said.
The enhanced risk that cancer patients face if they develop COVID-19 was documented in a recent review of 218 cancer patients hospitalized for COVID-19 during parts of March and April in a large New York health system. The results showed an overall mortality rate of 28%, including a 37% rate among 54 patients with hematologic malignancies and a 25% rate among 164 patients with solid tumors. The mortality rate “may not be quite as high as they reported because that depends on how many patients you test, but there is no question that patients with more comorbidities are at higher risk. Patients with active cancer on chemotherapy are a particularly vulnerable population, and many have expressed concerns about their vulnerability,” he observed.
For the few LCI patients who developed COVID-19 infection, the medical staff has had several therapeutic options they could match to each patient’s needs, with help from the Atrium Health infectious disease team. LCI and Atrium Health are participating in several COVID-19 clinical treatment trials, including an investigational convalescent plasma protocol spearheaded by the Mayo Clinic. They have also opened a randomized, phase 2 trial evaluating the safety and efficacy of selinexor (Xpovio), an oral drug that’s Food and Drug Administration approved for patients with multiple myeloma, for treatment of moderate or severe COVID-19 infection. Additional studies evaluating blockade of granulocyte-macrophage colony-stimulating factor, as well as inhaled antiviral therapy, have recently launched, and several additional studies are poised to open in the coming weeks.
The LCI and Atrium Health team also has a supply of the antiviral agent remdesivir as part of the FDA’s expanded access protocol and emergency use authorization. They also have a supply of and experience administering the interleukin-6 receptor inhibitor tocilizumab (Actemra), which showed some suggestion of efficacy in limited experience treating patients with severe or critical COVID-19 infections. Clinicians at LCI have not used the investigational and unproven agents hydroxychloroquine, chloroquine, and azithromycin to either prevent or treat COVID-19.
LCI also instituted measures to try to minimize the risk that staff members could become infected and transmit the virus while asymptomatic. Following conversations held early on with COVID-19–experienced health authorities in China and Italy, the patient-facing LCI staff split into two teams starting on March 23 that alternated responsibility for direct patient interactions every 2 weeks. When one of these teams was off from direct patient contact they continued to care for patients remotely through virtual technologies. The concept was that, if a staffer became infected while remaining asymptomatic during their contact with patients, their status would either become diagnosable or resolve during their 2 weeks away from seeing any patients. Perhaps in part because of this approach infections among staff members “have not been a big issue. We’ve had an incredibly low infection rate among the LCI staff,” Dr. Voorhees noted.
By mid-May, with the imminent threat of a sudden CODIV-19 surge moderated, heme-onc operations at LCI began to cautiously revert to more normal operations. “We’re continuing patient screening for signs and symptoms of COVID-19 infection, testing for asymptomatic infections, and requiring masking and social distancing in the clinics and hospitals, but we’re starting to slowly restore the number of patients at our clinics [virtual and face to face[ and infusion centers,” and the staff’s division into two teams ended. “The idea was to get past a surge and make sure our system was not overwhelmed. We anticipated a local surge in late April, but then it kept getting pushed back. Current projections are for the infection rate among LCI patients to remain low provided that community spread remains stable or, ideally, decreases.” The LCI infectious disease staff is closely monitoring infection rates for early recognition of an outbreak, with plans to follow any new cases with contact tracing. So far, the COVID-19 pandemic at LCI “has been very manageable,” Dr. Voorhees concluded.
“We’re now better positioned to deal with a case surge if it were to happen. We could resume the two-team approach, hospital-wide plans are now in place for a future surge, and we are now up and running with robust testing and inpatient and outpatient virtual technology. The first time, we were all learning on the fly.”
The LCI biostatistics team has been prospectively collecting the Institutes’s COVID-19 patient data, with plans to report their findings.
Dr. Voorhees has had financial relationships with Bristol-Myers Squibb/Celgene, Janssen, Novartis, and Oncopeptides, none of which are relevant to this article.
REACH2: Ruxolitinib outperformed control treatment for refractory acute GVHD
Ruxolitinib produced significantly better efficacy outcomes in patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD), compared with investigator’s choice of control therapy, in the phase 3 REACH2 trial.
However, there was a higher incidence of thrombocytopenia with ruxolitinib than with control treatment, according to a report by Robert Zeiser, MD, of University of Freiburg (Germany) and colleagues on behalf of the REACH2 research group. The report was published in the New England Journal of Medicine.
The REACH2 trial (NCT02913261) is a randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with investigator’s choice of therapy for control treatment using a list of nine commonly used options.
Patients were 12 years of age or older with glucocorticoid-refractory acute GVHD after allogeneic stem cell transplant. A total of 154 patients were assigned to the ruxolitinib group, and 155 patients were in the control group.
Most patients – 152 in the ruxolitinib group and 150 in the control group – received at least one dose of trial treatment.
Treatment discontinuation occurred in 72% (111/154) of patients in the ruxolitinib group and in 85% (132/155) of those in the control group. The most common reason for discontinuation was lack of efficacy (in 21% and 44%, respectively).
Outcomes
The overall response at day 28 (the primary endpoint) was significantly higher in the ruxolitinib group than in the control group (62% vs. 39%; odds ratio, 2.64; P < .001). The durable overall response at day 56 was also significantly higher in the ruxolitinib group than in the control group (40% vs. 22%; OR, 2.38; P < .001).
The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group compared with 39% in the control group.
The median failure-free survival was considerably longer with ruxolitinib than with control treatment (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non–relapse-related death, or the use of new systemic therapy for acute GVHD, 0.46).
The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (HR, 0.83).
Overall, 72 patients (47%) in the ruxolitinib group and 77 (51%) in the control group died by the data cutoff date. Most deaths were attributed to acute GVHD (22% in the ruxolitinib group and 25% in the control group).
The most common adverse events at day 28 (in the ruxolitinib and control arms, respectively) were thrombocytopenia (33% and 18%), anemia (30% and 28%), and cytomegalovirus infection (26% and 21%).
Praise for ‘successful’ randomized trial in GVHD
“The authors are to be congratulated for completing this successful randomized trial, which showed convincingly that ruxolitinib was more effective than the investigator’s choice of therapy ... in patients in whom glucocorticoid therapy had failed,” wrote Nelson Chao, MD, of Duke University in Durham, N.C., in his invited editorial.
He went on to speculate on the possible mechanism for ruxolitinib in these patients, discussing the possible role of the STAT3 and STAT1 signaling pathways.
Dr. Chao also found it “interesting that the incidence of infectious complications or relapse was apparently not greater with ruxolitinib than with control therapy,” but he noted that the total follow-up time was short.
“As with all good research, these observations raise important questions and set the stage for further work in this area,” he concluded.
The REACH2 trial was funded by Novartis. The study authors disclosed relationships with a variety of pharmaceutical companies, including Novartis. Dr. Chao reported having no relevant disclosures.
SOURCE: Zeiser R et al. N Engl J Med. 2020. doi: 10.1056/NEJMoa1917635.
Ruxolitinib produced significantly better efficacy outcomes in patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD), compared with investigator’s choice of control therapy, in the phase 3 REACH2 trial.
However, there was a higher incidence of thrombocytopenia with ruxolitinib than with control treatment, according to a report by Robert Zeiser, MD, of University of Freiburg (Germany) and colleagues on behalf of the REACH2 research group. The report was published in the New England Journal of Medicine.
The REACH2 trial (NCT02913261) is a randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with investigator’s choice of therapy for control treatment using a list of nine commonly used options.
Patients were 12 years of age or older with glucocorticoid-refractory acute GVHD after allogeneic stem cell transplant. A total of 154 patients were assigned to the ruxolitinib group, and 155 patients were in the control group.
Most patients – 152 in the ruxolitinib group and 150 in the control group – received at least one dose of trial treatment.
Treatment discontinuation occurred in 72% (111/154) of patients in the ruxolitinib group and in 85% (132/155) of those in the control group. The most common reason for discontinuation was lack of efficacy (in 21% and 44%, respectively).
Outcomes
The overall response at day 28 (the primary endpoint) was significantly higher in the ruxolitinib group than in the control group (62% vs. 39%; odds ratio, 2.64; P < .001). The durable overall response at day 56 was also significantly higher in the ruxolitinib group than in the control group (40% vs. 22%; OR, 2.38; P < .001).
The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group compared with 39% in the control group.
The median failure-free survival was considerably longer with ruxolitinib than with control treatment (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non–relapse-related death, or the use of new systemic therapy for acute GVHD, 0.46).
The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (HR, 0.83).
Overall, 72 patients (47%) in the ruxolitinib group and 77 (51%) in the control group died by the data cutoff date. Most deaths were attributed to acute GVHD (22% in the ruxolitinib group and 25% in the control group).
The most common adverse events at day 28 (in the ruxolitinib and control arms, respectively) were thrombocytopenia (33% and 18%), anemia (30% and 28%), and cytomegalovirus infection (26% and 21%).
Praise for ‘successful’ randomized trial in GVHD
“The authors are to be congratulated for completing this successful randomized trial, which showed convincingly that ruxolitinib was more effective than the investigator’s choice of therapy ... in patients in whom glucocorticoid therapy had failed,” wrote Nelson Chao, MD, of Duke University in Durham, N.C., in his invited editorial.
He went on to speculate on the possible mechanism for ruxolitinib in these patients, discussing the possible role of the STAT3 and STAT1 signaling pathways.
Dr. Chao also found it “interesting that the incidence of infectious complications or relapse was apparently not greater with ruxolitinib than with control therapy,” but he noted that the total follow-up time was short.
“As with all good research, these observations raise important questions and set the stage for further work in this area,” he concluded.
The REACH2 trial was funded by Novartis. The study authors disclosed relationships with a variety of pharmaceutical companies, including Novartis. Dr. Chao reported having no relevant disclosures.
SOURCE: Zeiser R et al. N Engl J Med. 2020. doi: 10.1056/NEJMoa1917635.
Ruxolitinib produced significantly better efficacy outcomes in patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD), compared with investigator’s choice of control therapy, in the phase 3 REACH2 trial.
However, there was a higher incidence of thrombocytopenia with ruxolitinib than with control treatment, according to a report by Robert Zeiser, MD, of University of Freiburg (Germany) and colleagues on behalf of the REACH2 research group. The report was published in the New England Journal of Medicine.
The REACH2 trial (NCT02913261) is a randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with investigator’s choice of therapy for control treatment using a list of nine commonly used options.
Patients were 12 years of age or older with glucocorticoid-refractory acute GVHD after allogeneic stem cell transplant. A total of 154 patients were assigned to the ruxolitinib group, and 155 patients were in the control group.
Most patients – 152 in the ruxolitinib group and 150 in the control group – received at least one dose of trial treatment.
Treatment discontinuation occurred in 72% (111/154) of patients in the ruxolitinib group and in 85% (132/155) of those in the control group. The most common reason for discontinuation was lack of efficacy (in 21% and 44%, respectively).
Outcomes
The overall response at day 28 (the primary endpoint) was significantly higher in the ruxolitinib group than in the control group (62% vs. 39%; odds ratio, 2.64; P < .001). The durable overall response at day 56 was also significantly higher in the ruxolitinib group than in the control group (40% vs. 22%; OR, 2.38; P < .001).
The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group compared with 39% in the control group.
The median failure-free survival was considerably longer with ruxolitinib than with control treatment (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non–relapse-related death, or the use of new systemic therapy for acute GVHD, 0.46).
The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (HR, 0.83).
Overall, 72 patients (47%) in the ruxolitinib group and 77 (51%) in the control group died by the data cutoff date. Most deaths were attributed to acute GVHD (22% in the ruxolitinib group and 25% in the control group).
The most common adverse events at day 28 (in the ruxolitinib and control arms, respectively) were thrombocytopenia (33% and 18%), anemia (30% and 28%), and cytomegalovirus infection (26% and 21%).
Praise for ‘successful’ randomized trial in GVHD
“The authors are to be congratulated for completing this successful randomized trial, which showed convincingly that ruxolitinib was more effective than the investigator’s choice of therapy ... in patients in whom glucocorticoid therapy had failed,” wrote Nelson Chao, MD, of Duke University in Durham, N.C., in his invited editorial.
He went on to speculate on the possible mechanism for ruxolitinib in these patients, discussing the possible role of the STAT3 and STAT1 signaling pathways.
Dr. Chao also found it “interesting that the incidence of infectious complications or relapse was apparently not greater with ruxolitinib than with control therapy,” but he noted that the total follow-up time was short.
“As with all good research, these observations raise important questions and set the stage for further work in this area,” he concluded.
The REACH2 trial was funded by Novartis. The study authors disclosed relationships with a variety of pharmaceutical companies, including Novartis. Dr. Chao reported having no relevant disclosures.
SOURCE: Zeiser R et al. N Engl J Med. 2020. doi: 10.1056/NEJMoa1917635.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Ruxolitinib was significantly more effective against acute graft-versus-host disease than was control treatment.
Major finding: The overall response at day 28 was significantly higher in the ruxolitinib group than in the control group (62% vs. 39%; P < .001).
Study details: Phase 3 trial of 154 patients randomized to ruxolitinib and 155 patients randomized to investigator’s choice of control therapy.
Disclosures: The trial was funded by Novartis. Authors disclosed relationships with a variety of pharmaceutical companies, including Novartis.
Source: Zeiser R et al. N Engl J Med. 2020. doi: 10.1056/NEJMoa1917635.
Phase 2 study shows regimen benefit with dasatinib in Ph+ALL therapy
ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.
Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.
The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.
After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.
The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.
However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.
JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.
“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.
Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.
Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m2 of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.
Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.
Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.
Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.
Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.
At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.
Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.
MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.
“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.
The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.
Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.
This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.
SOURCE: Sugiura I et al. ASH 2019. Abstract 743.
ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.
Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.
The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.
After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.
The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.
However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.
JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.
“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.
Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.
Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m2 of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.
Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.
Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.
Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.
Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.
At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.
Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.
MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.
“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.
The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.
Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.
This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.
SOURCE: Sugiura I et al. ASH 2019. Abstract 743.
ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.
Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.
The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.
After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.
The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.
However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.
JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.
“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.
Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.
Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m2 of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.
Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.
Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.
Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.
Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.
At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.
Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.
MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.
“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.
The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.
Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.
This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.
SOURCE: Sugiura I et al. ASH 2019. Abstract 743.
REPORTING FROM ASH 2019
CAR T-cell therapy may worsen mental health in some patients
Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.
But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.
These findings provide clinical insight into a minimally researched patient population.
“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”
The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.
Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.
Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.
“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.
SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.
Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.
But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.
These findings provide clinical insight into a minimally researched patient population.
“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”
The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.
Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.
Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.
“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.
SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.
Chimeric antigen receptor (CAR) T-cell therapy is generally associated with good long-term neuropsychiatric status, based on a recent patient-reported outcomes study.
But almost one out of five patients may have notably worse cognitive and psychiatric outcomes within 1-5 years of therapy, reported Julia Ruark, MD, of the University of Washington, Seattle, and colleagues. According to Dr. Ruark and associates, this latter finding suggests that CAR T-cell therapy may negatively impact mental health in a subset of patients.
These findings provide clinical insight into a minimally researched patient population.
“At this time, only limited data are available regarding the long-term effects of CAR T-cell therapy,” the investigators wrote in Biology of Blood and Marrow Transplantation. “Thus, it is important to evaluate the late neuropsychiatric effects of CAR T and evaluate their effect on survivors’ quality of life.”
The study involved 40 patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. Before undergoing CAR T-cell therapy, patients underwent standardized mental health screening with validated instruments such as the 7-item Generalized Anxiety Disorder scale. At least 1 year after CAR T-cell therapy, patients completed a questionnaire consisting of the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.2 Global Health and the PROMIS-29 Profile v2.1, and 30 additional questions, 4 of which evaluated cognitive function. These data were converted to T scores for comparative purposes.
Patients who underwent CAR T-cell therapy had statistically similar T scores to the general population mean, suggesting comparable overall neuropsychiatric status. However, a closer look at the data showed that almost one out of five patients who underwent CAR T-cell therapy had global mental health scores that were at least 1 standard deviation lower than the mean for the general population and patients with cancer.
Almost half of the patients (47.5%) who underwent CAR T-cell therapy reported at least one clinically meaningful negative neuropsychiatric outcome. Specifically, 20% reported cognitive difficulties and depression or anxiety, 17.5% reported cognitive difficulties without depression or anxiety, and 10% reported depression or anxiety without cognitive difficulties. One-quarter (25%) of patients reported taking a medication for depression, 20% reported use of anxiolytics, and 15% reported use of sleep medications. Multivariate analysis revealed an association between younger age and depression (P = .01), anxiety (P = .001), and worse long-term global mental health (P = .02). Cognitive difficulties were significantly more common among patients with worse physical and/or mental health.
“[A] subset of patients may experience psychiatric symptoms or cognitive impairment [which may be related to CAR T-cell therapy or other treatments patients have been exposed to], and it is important to identify those patients to assist with intervention strategies,” the investigators concluded.The study was funded by the National Institutes of Health, Life Science Discovery Fund, Juno Therapeutics/Celgene, and others. The investigators reported additional relationships with Nektar Therapeutics, Allogene Therapeutics, T-CURX, and others.
SOURCE: Ruark J et al. Biol Blood Marrow Transplant. 2019 Oct 9. doi: 10.1016/j.bbmt.2019.09.037.
FROM BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Several factors may drive recent improvements in allo-HCT outcomes
A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.
Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.
Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.
“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.
“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
Baseline characteristics and treatment
Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.
Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.
Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.
The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).
GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
Outcomes
Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).
Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).
Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
Potential drivers of outcome
Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.
Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”
The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”
“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”
Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.
“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”
Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.
This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.
SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.
Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.
Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.
“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.
“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
Baseline characteristics and treatment
Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.
Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.
Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.
The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).
GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
Outcomes
Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).
Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).
Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
Potential drivers of outcome
Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.
Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”
The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”
“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”
Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.
“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”
Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.
This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.
SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.
Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.
Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.
“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.
“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
Baseline characteristics and treatment
Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.
Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.
Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.
The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).
GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
Outcomes
Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).
Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).
Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
Potential drivers of outcome
Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.
Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”
The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”
“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”
Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.
“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”
Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.
This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.
SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point: At a single center, outcomes of allogeneic hematopoietic cell transplant improved for patients treated in 2013-2017, compared with patients treated in 2003-2007.
Major finding: Rates of nonrelapse mortality at day 200 were higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).
Study details: A single-center study of 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.
Disclosures: The research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.
Source: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
PT-Cy bests conventional GVHD prophylaxis
ORLANDO – Posttransplant cyclophosphamide may be superior to conventional immunosuppression as graft-versus-host disease prophylaxis, according to findings presented at the annual meeting of the American Society of Hematology.
A phase 3 trial showed that posttransplant cyclophosphamide (PT-Cy) reduced graft-versus-host disease (GVHD) without affecting relapse. Rates of acute and chronic GVHD were significantly lower among patients who received PT-Cy than among those who received conventional immunosuppression (CIS). Rates of progression/relapse, progression-free survival, and overall survival were similar between the PT-Cy and CIS arms.
These results suggest PT-Cy provides a “long-term benefit and positive impact on quality of life” for patients undergoing allogeneic hematopoietic stem cell transplant, according to Annoek E.C. Broers, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. Dr. Broers presented the results during the plenary session at ASH 2019.
The trial enrolled 160 patients with leukemias, lymphomas, myelomas, and other hematologic malignancies. All patients had a matched, related donor or an 8/8 or greater matched, unrelated donor.
The patients were randomized to receive CIS (n = 55) or PT-Cy (n = 105) as GVHD prophylaxis. The CIS regimen consisted of cyclosporine A (from day –3 to 180) and mycophenolic acid (from day 0 to 84). Patients in the PT-Cy arm received cyclophosphamide at 50 mg/kg (days 3 and 4) and cyclosporine A (from day 5 to 70).
Baseline characteristics were similar between the treatment arms. The median age was 58 years in the CIS arm and 57 years in the PT-Cy arm. A majority of patients were men – 63% and 67%, respectively.
Two patients in the CIS arm received myeloablative conditioning, but all other patients received reduced-intensity conditioning. Most patients in the CIS arm (67%) and the PT-Cy arm (70%) had a matched, unrelated donor. All patients in the CIS arm and 96% in the PT-Cy arm received peripheral blood cell grafts.
PT-Cy significantly reduced the cumulative incidence of acute and chronic GVHD. The incidence of grade 2-4 acute GVHD at 6 months was 48% in the CIS arm and 32% in the PT-Cy arm (P = .014). The incidence of chronic extensive GVHD at 24 months was 50% and 19%, respectively (P = .001).
There were no significant between-arm differences for any other individual endpoint assessed.
“With a median follow-up of 3.2 years, so far, there’s no difference in the cumulative incidence of progression or relapse, nor is there a difference in progression-free or overall survival,” Dr. Broers said.
At 60 months, the rate of relapse/progression was 32% in the PT-Cy arm and 26% in the CIS arm (P = .36). The rate of nonrelapse mortality was 11% and 14%, respectively (P = .53).
At 60 months, the progression-free survival was 60% in the CIS arm and 58% in the PT-Cy arm (P = .67). The overall survival was 69% and 63%, respectively (P = .63).
In addition to assessing endpoints that “determine the success of our transplant strategy,” Dr. Broers said she and her colleagues also looked at a combined endpoint to account for “the effect GVHD has on morbidity and quality of life.” That endpoint is GVHD- and relapse-free survival.
The researchers found that PT-Cy improved GVHD- and relapse-free survival at 12 months. It was 22% in the CIS arm and 45% in the PT-Cy arm (P = .001). PT-Cy conferred this benefit irrespective of donor type, Dr. Broers noted.
Overall, the incidence of adverse events was somewhat higher in the PT-Cy arm (60%) than in the CIS arm (42%). The incidence of infections also was higher in the PT-Cy arm (41%) than in the CIS arm (21%), and this was largely caused by a greater incidence of neutropenic fever with PT-Cy (25% vs. 15%).
The study was funded by the Dutch Cancer Society, and Novartis provided the mycophenolic acid used in the study. Dr. Broers reported having no conflicts of interest.
SOURCE: Broers AEC et al. ASH 2019, Abstract 1.
ORLANDO – Posttransplant cyclophosphamide may be superior to conventional immunosuppression as graft-versus-host disease prophylaxis, according to findings presented at the annual meeting of the American Society of Hematology.
A phase 3 trial showed that posttransplant cyclophosphamide (PT-Cy) reduced graft-versus-host disease (GVHD) without affecting relapse. Rates of acute and chronic GVHD were significantly lower among patients who received PT-Cy than among those who received conventional immunosuppression (CIS). Rates of progression/relapse, progression-free survival, and overall survival were similar between the PT-Cy and CIS arms.
These results suggest PT-Cy provides a “long-term benefit and positive impact on quality of life” for patients undergoing allogeneic hematopoietic stem cell transplant, according to Annoek E.C. Broers, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. Dr. Broers presented the results during the plenary session at ASH 2019.
The trial enrolled 160 patients with leukemias, lymphomas, myelomas, and other hematologic malignancies. All patients had a matched, related donor or an 8/8 or greater matched, unrelated donor.
The patients were randomized to receive CIS (n = 55) or PT-Cy (n = 105) as GVHD prophylaxis. The CIS regimen consisted of cyclosporine A (from day –3 to 180) and mycophenolic acid (from day 0 to 84). Patients in the PT-Cy arm received cyclophosphamide at 50 mg/kg (days 3 and 4) and cyclosporine A (from day 5 to 70).
Baseline characteristics were similar between the treatment arms. The median age was 58 years in the CIS arm and 57 years in the PT-Cy arm. A majority of patients were men – 63% and 67%, respectively.
Two patients in the CIS arm received myeloablative conditioning, but all other patients received reduced-intensity conditioning. Most patients in the CIS arm (67%) and the PT-Cy arm (70%) had a matched, unrelated donor. All patients in the CIS arm and 96% in the PT-Cy arm received peripheral blood cell grafts.
PT-Cy significantly reduced the cumulative incidence of acute and chronic GVHD. The incidence of grade 2-4 acute GVHD at 6 months was 48% in the CIS arm and 32% in the PT-Cy arm (P = .014). The incidence of chronic extensive GVHD at 24 months was 50% and 19%, respectively (P = .001).
There were no significant between-arm differences for any other individual endpoint assessed.
“With a median follow-up of 3.2 years, so far, there’s no difference in the cumulative incidence of progression or relapse, nor is there a difference in progression-free or overall survival,” Dr. Broers said.
At 60 months, the rate of relapse/progression was 32% in the PT-Cy arm and 26% in the CIS arm (P = .36). The rate of nonrelapse mortality was 11% and 14%, respectively (P = .53).
At 60 months, the progression-free survival was 60% in the CIS arm and 58% in the PT-Cy arm (P = .67). The overall survival was 69% and 63%, respectively (P = .63).
In addition to assessing endpoints that “determine the success of our transplant strategy,” Dr. Broers said she and her colleagues also looked at a combined endpoint to account for “the effect GVHD has on morbidity and quality of life.” That endpoint is GVHD- and relapse-free survival.
The researchers found that PT-Cy improved GVHD- and relapse-free survival at 12 months. It was 22% in the CIS arm and 45% in the PT-Cy arm (P = .001). PT-Cy conferred this benefit irrespective of donor type, Dr. Broers noted.
Overall, the incidence of adverse events was somewhat higher in the PT-Cy arm (60%) than in the CIS arm (42%). The incidence of infections also was higher in the PT-Cy arm (41%) than in the CIS arm (21%), and this was largely caused by a greater incidence of neutropenic fever with PT-Cy (25% vs. 15%).
The study was funded by the Dutch Cancer Society, and Novartis provided the mycophenolic acid used in the study. Dr. Broers reported having no conflicts of interest.
SOURCE: Broers AEC et al. ASH 2019, Abstract 1.
ORLANDO – Posttransplant cyclophosphamide may be superior to conventional immunosuppression as graft-versus-host disease prophylaxis, according to findings presented at the annual meeting of the American Society of Hematology.
A phase 3 trial showed that posttransplant cyclophosphamide (PT-Cy) reduced graft-versus-host disease (GVHD) without affecting relapse. Rates of acute and chronic GVHD were significantly lower among patients who received PT-Cy than among those who received conventional immunosuppression (CIS). Rates of progression/relapse, progression-free survival, and overall survival were similar between the PT-Cy and CIS arms.
These results suggest PT-Cy provides a “long-term benefit and positive impact on quality of life” for patients undergoing allogeneic hematopoietic stem cell transplant, according to Annoek E.C. Broers, MD, PhD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands. Dr. Broers presented the results during the plenary session at ASH 2019.
The trial enrolled 160 patients with leukemias, lymphomas, myelomas, and other hematologic malignancies. All patients had a matched, related donor or an 8/8 or greater matched, unrelated donor.
The patients were randomized to receive CIS (n = 55) or PT-Cy (n = 105) as GVHD prophylaxis. The CIS regimen consisted of cyclosporine A (from day –3 to 180) and mycophenolic acid (from day 0 to 84). Patients in the PT-Cy arm received cyclophosphamide at 50 mg/kg (days 3 and 4) and cyclosporine A (from day 5 to 70).
Baseline characteristics were similar between the treatment arms. The median age was 58 years in the CIS arm and 57 years in the PT-Cy arm. A majority of patients were men – 63% and 67%, respectively.
Two patients in the CIS arm received myeloablative conditioning, but all other patients received reduced-intensity conditioning. Most patients in the CIS arm (67%) and the PT-Cy arm (70%) had a matched, unrelated donor. All patients in the CIS arm and 96% in the PT-Cy arm received peripheral blood cell grafts.
PT-Cy significantly reduced the cumulative incidence of acute and chronic GVHD. The incidence of grade 2-4 acute GVHD at 6 months was 48% in the CIS arm and 32% in the PT-Cy arm (P = .014). The incidence of chronic extensive GVHD at 24 months was 50% and 19%, respectively (P = .001).
There were no significant between-arm differences for any other individual endpoint assessed.
“With a median follow-up of 3.2 years, so far, there’s no difference in the cumulative incidence of progression or relapse, nor is there a difference in progression-free or overall survival,” Dr. Broers said.
At 60 months, the rate of relapse/progression was 32% in the PT-Cy arm and 26% in the CIS arm (P = .36). The rate of nonrelapse mortality was 11% and 14%, respectively (P = .53).
At 60 months, the progression-free survival was 60% in the CIS arm and 58% in the PT-Cy arm (P = .67). The overall survival was 69% and 63%, respectively (P = .63).
In addition to assessing endpoints that “determine the success of our transplant strategy,” Dr. Broers said she and her colleagues also looked at a combined endpoint to account for “the effect GVHD has on morbidity and quality of life.” That endpoint is GVHD- and relapse-free survival.
The researchers found that PT-Cy improved GVHD- and relapse-free survival at 12 months. It was 22% in the CIS arm and 45% in the PT-Cy arm (P = .001). PT-Cy conferred this benefit irrespective of donor type, Dr. Broers noted.
Overall, the incidence of adverse events was somewhat higher in the PT-Cy arm (60%) than in the CIS arm (42%). The incidence of infections also was higher in the PT-Cy arm (41%) than in the CIS arm (21%), and this was largely caused by a greater incidence of neutropenic fever with PT-Cy (25% vs. 15%).
The study was funded by the Dutch Cancer Society, and Novartis provided the mycophenolic acid used in the study. Dr. Broers reported having no conflicts of interest.
SOURCE: Broers AEC et al. ASH 2019, Abstract 1.
REPORTING FROM ASH 2019
Myeloma patients over age 70 can benefit from auto-HC transplant
ORLANDO – Age 70 may be the new 60, at least when it comes to outcomes following autologous hematopoietic cell transplantation (auto-HCT) in multiple myeloma.
A large-scale study looking at transplant outcomes across age groups in multiple myeloma patients found similar rates of nonrelapse mortality, relapse/progression, progression-free survival, and overall survival between patients who were aged 70 years and older and those who were aged 60-69 years.
“Age has no implication in terms of the antimyeloma effect of transplant,” Anita D’Souza, MD, of the Medical College of Wisconsin, Milwaukee, said at the annual meeting of the American Society of Hematology.
The study analyzed outcomes from 15,999 multiple myeloma patients aged 20 years or older in the United States who received a single auto-HCT with melphalan conditioning within 12 months of diagnosis between 2013 and 2017. Within that dataset, the researchers compared outcomes from 7,032 patients aged 60-69 years and 2,092 patients aged 70 years and older.
This is the largest study of auto-HCT in older adults with multiple myeloma, the researchers said, and provides important data about the benefit of transplant at any age.
Univariate analysis showed that 100-day nonrelapse mortality was higher in patients aged 70 years and older – at 1% – compared with younger patients (P less than .01). Also, 2-year overall survival was lower in older adults – at 86% – compared with 60- to 69-year-olds (P less than .01).
However, on multivariate analysis with 60- to 69-year-olds as the reference group, patients older than age 70 years had similar nonrelapse mortality (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1, 1.7, P = .06). The same trends were seen for relapse/progression (HR 1.0, 95% CI, 0.9-1, P = .6), progression-free survival (HR 1.1, 95% CI 1-1.2, P = .2), and overall survival (HR 1.2, 95% CI 1-1.4, P = .03). Given the large sample size, a P value of .01 was considered statistically significant.
Over the course of the study period, the percentage of patients aged 70 and older who received a transplant grew each year, rising to 28% by 2017. But Dr. D’Souza said that number is still too low given the safety and efficacy of auto-HCT in these patients.
“Every patient with myeloma should be referred to a transplant center,” she said.
Dr. D’Souza reported financial disclosures related to EDO-Mundapharma, Merck, Prothena, Sanofi, TeneoBio, Prothena, Pfizer, Imbrium, and Akcea. Other study authors reported financial relationships with multiple companies including Celgene, Takeda, BMS, and Janssen.
SOURCE: Munshi PN et al. ASH 2019, Abstract 782.
ORLANDO – Age 70 may be the new 60, at least when it comes to outcomes following autologous hematopoietic cell transplantation (auto-HCT) in multiple myeloma.
A large-scale study looking at transplant outcomes across age groups in multiple myeloma patients found similar rates of nonrelapse mortality, relapse/progression, progression-free survival, and overall survival between patients who were aged 70 years and older and those who were aged 60-69 years.
“Age has no implication in terms of the antimyeloma effect of transplant,” Anita D’Souza, MD, of the Medical College of Wisconsin, Milwaukee, said at the annual meeting of the American Society of Hematology.
The study analyzed outcomes from 15,999 multiple myeloma patients aged 20 years or older in the United States who received a single auto-HCT with melphalan conditioning within 12 months of diagnosis between 2013 and 2017. Within that dataset, the researchers compared outcomes from 7,032 patients aged 60-69 years and 2,092 patients aged 70 years and older.
This is the largest study of auto-HCT in older adults with multiple myeloma, the researchers said, and provides important data about the benefit of transplant at any age.
Univariate analysis showed that 100-day nonrelapse mortality was higher in patients aged 70 years and older – at 1% – compared with younger patients (P less than .01). Also, 2-year overall survival was lower in older adults – at 86% – compared with 60- to 69-year-olds (P less than .01).
However, on multivariate analysis with 60- to 69-year-olds as the reference group, patients older than age 70 years had similar nonrelapse mortality (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1, 1.7, P = .06). The same trends were seen for relapse/progression (HR 1.0, 95% CI, 0.9-1, P = .6), progression-free survival (HR 1.1, 95% CI 1-1.2, P = .2), and overall survival (HR 1.2, 95% CI 1-1.4, P = .03). Given the large sample size, a P value of .01 was considered statistically significant.
Over the course of the study period, the percentage of patients aged 70 and older who received a transplant grew each year, rising to 28% by 2017. But Dr. D’Souza said that number is still too low given the safety and efficacy of auto-HCT in these patients.
“Every patient with myeloma should be referred to a transplant center,” she said.
Dr. D’Souza reported financial disclosures related to EDO-Mundapharma, Merck, Prothena, Sanofi, TeneoBio, Prothena, Pfizer, Imbrium, and Akcea. Other study authors reported financial relationships with multiple companies including Celgene, Takeda, BMS, and Janssen.
SOURCE: Munshi PN et al. ASH 2019, Abstract 782.
ORLANDO – Age 70 may be the new 60, at least when it comes to outcomes following autologous hematopoietic cell transplantation (auto-HCT) in multiple myeloma.
A large-scale study looking at transplant outcomes across age groups in multiple myeloma patients found similar rates of nonrelapse mortality, relapse/progression, progression-free survival, and overall survival between patients who were aged 70 years and older and those who were aged 60-69 years.
“Age has no implication in terms of the antimyeloma effect of transplant,” Anita D’Souza, MD, of the Medical College of Wisconsin, Milwaukee, said at the annual meeting of the American Society of Hematology.
The study analyzed outcomes from 15,999 multiple myeloma patients aged 20 years or older in the United States who received a single auto-HCT with melphalan conditioning within 12 months of diagnosis between 2013 and 2017. Within that dataset, the researchers compared outcomes from 7,032 patients aged 60-69 years and 2,092 patients aged 70 years and older.
This is the largest study of auto-HCT in older adults with multiple myeloma, the researchers said, and provides important data about the benefit of transplant at any age.
Univariate analysis showed that 100-day nonrelapse mortality was higher in patients aged 70 years and older – at 1% – compared with younger patients (P less than .01). Also, 2-year overall survival was lower in older adults – at 86% – compared with 60- to 69-year-olds (P less than .01).
However, on multivariate analysis with 60- to 69-year-olds as the reference group, patients older than age 70 years had similar nonrelapse mortality (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1, 1.7, P = .06). The same trends were seen for relapse/progression (HR 1.0, 95% CI, 0.9-1, P = .6), progression-free survival (HR 1.1, 95% CI 1-1.2, P = .2), and overall survival (HR 1.2, 95% CI 1-1.4, P = .03). Given the large sample size, a P value of .01 was considered statistically significant.
Over the course of the study period, the percentage of patients aged 70 and older who received a transplant grew each year, rising to 28% by 2017. But Dr. D’Souza said that number is still too low given the safety and efficacy of auto-HCT in these patients.
“Every patient with myeloma should be referred to a transplant center,” she said.
Dr. D’Souza reported financial disclosures related to EDO-Mundapharma, Merck, Prothena, Sanofi, TeneoBio, Prothena, Pfizer, Imbrium, and Akcea. Other study authors reported financial relationships with multiple companies including Celgene, Takeda, BMS, and Janssen.
SOURCE: Munshi PN et al. ASH 2019, Abstract 782.
REPORTING FROM ASH 2019
Case-control study IDs several novel risk factors of post-HCT melanoma
(HCT), according to findings from a nested case-control study.
The study included 140 cases of melanoma and 557 controls matched by age at HCT, sex, primary disease, and survival time. The results showed a significantly increased melanoma risk in HCT survivors who received total body irradiation–based myeloablative conditioning, reduced-intensity conditioning with melphalan, or reduced-intensity conditioning with fludarabine, compared with those who received busulfan-based myeloablative conditioning (odds ratios, 1.77, 2.60, and 2.72, respectively), Megan M. Herr, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, and the Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues reported in the Journal of the American Academy of Dermatology.
Melanoma risk also was increased in patients who experienced acute graft-versus-host disease (GVHD) with stage 2 or greater skin involvement (OR, 1.92 vs. those with no acute GVHD), chronic GVHD without skin involvement (OR, 1.91 vs. those with no chronic GVHD), or keratinocytic carcinoma (OR, 2.37), and in those who resided in areas with higher ambient ultraviolet radiation (OR for the highest vs. lowest tertile, 1.64).
The UV radiation finding was more pronounced for melanomas occurring 6 or more years after transplant (OR, 3.04 for highest vs. lowest tertile), whereas ambient UV radiation was not associated with melanomas occurring earlier (ORs, 1.37 for less than 3 years and 0.98 at 3-6 years), the investigators noted.
The findings, based on large-scale and detailed clinical data from the Center for International Blood and Marrow Transplant Research for HCT performed during 1985-2012, show that melanoma after HCT has a multifactorial etiology that includes patient-, transplant-, and posttransplant-related factors, they said, noting that the findings also underscore the importance of “prioritization of high-risk survivors for adherence to prevention and screening recommendations.”
Those recommendations call for routine skin examination and photoprotective precautions – particularly in HCT survivors at the highest risk – but studies of screening behaviors suggest that fewer than two-thirds of HCT survivors adhere to these recommendations, they said, concluding that further research on the cost-effectiveness of melanoma screening is warranted, as is investigation into whether current approaches are associated with melanoma risk.
This work was supported by the intramural research program of the National Cancer Institute, the National Institutes of Health, and the Department of Health & Human Services. The authors reported having no conflicts of interest.
SOURCE: Herr MM et al. J Am Acad Dermatol. 2019 Oct 22. doi: 10.1016/j.jaad.2019.10.034.
(HCT), according to findings from a nested case-control study.
The study included 140 cases of melanoma and 557 controls matched by age at HCT, sex, primary disease, and survival time. The results showed a significantly increased melanoma risk in HCT survivors who received total body irradiation–based myeloablative conditioning, reduced-intensity conditioning with melphalan, or reduced-intensity conditioning with fludarabine, compared with those who received busulfan-based myeloablative conditioning (odds ratios, 1.77, 2.60, and 2.72, respectively), Megan M. Herr, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, and the Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues reported in the Journal of the American Academy of Dermatology.
Melanoma risk also was increased in patients who experienced acute graft-versus-host disease (GVHD) with stage 2 or greater skin involvement (OR, 1.92 vs. those with no acute GVHD), chronic GVHD without skin involvement (OR, 1.91 vs. those with no chronic GVHD), or keratinocytic carcinoma (OR, 2.37), and in those who resided in areas with higher ambient ultraviolet radiation (OR for the highest vs. lowest tertile, 1.64).
The UV radiation finding was more pronounced for melanomas occurring 6 or more years after transplant (OR, 3.04 for highest vs. lowest tertile), whereas ambient UV radiation was not associated with melanomas occurring earlier (ORs, 1.37 for less than 3 years and 0.98 at 3-6 years), the investigators noted.
The findings, based on large-scale and detailed clinical data from the Center for International Blood and Marrow Transplant Research for HCT performed during 1985-2012, show that melanoma after HCT has a multifactorial etiology that includes patient-, transplant-, and posttransplant-related factors, they said, noting that the findings also underscore the importance of “prioritization of high-risk survivors for adherence to prevention and screening recommendations.”
Those recommendations call for routine skin examination and photoprotective precautions – particularly in HCT survivors at the highest risk – but studies of screening behaviors suggest that fewer than two-thirds of HCT survivors adhere to these recommendations, they said, concluding that further research on the cost-effectiveness of melanoma screening is warranted, as is investigation into whether current approaches are associated with melanoma risk.
This work was supported by the intramural research program of the National Cancer Institute, the National Institutes of Health, and the Department of Health & Human Services. The authors reported having no conflicts of interest.
SOURCE: Herr MM et al. J Am Acad Dermatol. 2019 Oct 22. doi: 10.1016/j.jaad.2019.10.034.
(HCT), according to findings from a nested case-control study.
The study included 140 cases of melanoma and 557 controls matched by age at HCT, sex, primary disease, and survival time. The results showed a significantly increased melanoma risk in HCT survivors who received total body irradiation–based myeloablative conditioning, reduced-intensity conditioning with melphalan, or reduced-intensity conditioning with fludarabine, compared with those who received busulfan-based myeloablative conditioning (odds ratios, 1.77, 2.60, and 2.72, respectively), Megan M. Herr, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, and the Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues reported in the Journal of the American Academy of Dermatology.
Melanoma risk also was increased in patients who experienced acute graft-versus-host disease (GVHD) with stage 2 or greater skin involvement (OR, 1.92 vs. those with no acute GVHD), chronic GVHD without skin involvement (OR, 1.91 vs. those with no chronic GVHD), or keratinocytic carcinoma (OR, 2.37), and in those who resided in areas with higher ambient ultraviolet radiation (OR for the highest vs. lowest tertile, 1.64).
The UV radiation finding was more pronounced for melanomas occurring 6 or more years after transplant (OR, 3.04 for highest vs. lowest tertile), whereas ambient UV radiation was not associated with melanomas occurring earlier (ORs, 1.37 for less than 3 years and 0.98 at 3-6 years), the investigators noted.
The findings, based on large-scale and detailed clinical data from the Center for International Blood and Marrow Transplant Research for HCT performed during 1985-2012, show that melanoma after HCT has a multifactorial etiology that includes patient-, transplant-, and posttransplant-related factors, they said, noting that the findings also underscore the importance of “prioritization of high-risk survivors for adherence to prevention and screening recommendations.”
Those recommendations call for routine skin examination and photoprotective precautions – particularly in HCT survivors at the highest risk – but studies of screening behaviors suggest that fewer than two-thirds of HCT survivors adhere to these recommendations, they said, concluding that further research on the cost-effectiveness of melanoma screening is warranted, as is investigation into whether current approaches are associated with melanoma risk.
This work was supported by the intramural research program of the National Cancer Institute, the National Institutes of Health, and the Department of Health & Human Services. The authors reported having no conflicts of interest.
SOURCE: Herr MM et al. J Am Acad Dermatol. 2019 Oct 22. doi: 10.1016/j.jaad.2019.10.034.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY