Transplantation

HOUSTON – Lentiviral gene therapy appears safe and was potentially effective in a rare primary immunodeficiency disease known as X-linked chronic granulomatous disease, said Donald B. Kohn, MD, of the University of California, Los Angeles.

Seven of nine patients treated were “alive and well” at 12 months’ follow-up after receiving lentiviral vector transduced CD34+ cells, Dr. Kohn reported in a late-breaking clinical trial session at the Transplantation & Cellular Therapy Meetings.

Most patients were able to discontinue antibiotic prophylaxis for this disease, which is associated with severe, recurrent, and prolonged life-threatening infections, he said.

Results of the small study provide “proof of concept” for use of the gene therapy in the disease, though additional studies are needed to formally assess the clinical safety and efficacy of the approach, he said.

The estimated incidence of chronic granulomatous disease is 1 in 200,000 births in the United States, and the X-linked form is most common, occurring in about 60% of patients, Dr. Kohn told attendees of the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Most of these patients are treated with antibacterial or antifungal prophylaxis. While allogeneic hematopoietic stem cell transplantation is also an option, according to Dr. Kohn, the approach is limited by a lack of matched donors and graft-versus-host disease.

Dr. Kohn reported results for nine patients in the United States and the United Kingdom who were treated with the same G1XCGD lentiviral vector. The patients, who ranged in age from 2 to 27 years, underwent CD34+ cell mobilization or bone marrow isolation, transduction with the lentiviral vector, busulfan conditioning, and autologous transplantation.

All patients had confirmed X-linked chronic granulomatous disease, and had had at least one severe infection or inflammatory complication requiring hospitalization.

There were no infusion-related adverse events, and one serious adverse event, which was an inflammatory syndrome that resolved with steroids. Two patients died from complications unrelated to gene therapy, Dr. Kohn reported.

“The other patients are basically doing quite well,” he said.

Of the seven patients alive at the 12-month follow up, six were reported as “clinically well” and off antibiotic prophylaxis, according to Dr. Kohn, while the seventh patient was clinically well and receiving antimicrobial support.

Dr. Kohn is a scientific advisory board member for Orchard Therapeutics, which licensed the lentiviral gene therapy for X-CGD discussed in his presentation. He is also an inventor of intellectual property related to the therapy that UCLA has licensed to Orchard.

At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

SOURCE: Kohn DB et al. TCT 2019, Abstract LBA1.

HOUSTON – Lentiviral gene therapy appears safe and was potentially effective in a rare primary immunodeficiency disease known as X-linked chronic granulomatous disease, said Donald B. Kohn, MD, of the University of California, Los Angeles.

Seven of nine patients treated were “alive and well” at 12 months’ follow-up after receiving lentiviral vector transduced CD34+ cells, Dr. Kohn reported in a late-breaking clinical trial session at the Transplantation & Cellular Therapy Meetings.

Most patients were able to discontinue antibiotic prophylaxis for this disease, which is associated with severe, recurrent, and prolonged life-threatening infections, he said.

Results of the small study provide “proof of concept” for use of the gene therapy in the disease, though additional studies are needed to formally assess the clinical safety and efficacy of the approach, he said.

The estimated incidence of chronic granulomatous disease is 1 in 200,000 births in the United States, and the X-linked form is most common, occurring in about 60% of patients, Dr. Kohn told attendees of the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Most of these patients are treated with antibacterial or antifungal prophylaxis. While allogeneic hematopoietic stem cell transplantation is also an option, according to Dr. Kohn, the approach is limited by a lack of matched donors and graft-versus-host disease.

Dr. Kohn reported results for nine patients in the United States and the United Kingdom who were treated with the same G1XCGD lentiviral vector. The patients, who ranged in age from 2 to 27 years, underwent CD34+ cell mobilization or bone marrow isolation, transduction with the lentiviral vector, busulfan conditioning, and autologous transplantation.

All patients had confirmed X-linked chronic granulomatous disease, and had had at least one severe infection or inflammatory complication requiring hospitalization.

There were no infusion-related adverse events, and one serious adverse event, which was an inflammatory syndrome that resolved with steroids. Two patients died from complications unrelated to gene therapy, Dr. Kohn reported.

“The other patients are basically doing quite well,” he said.

Of the seven patients alive at the 12-month follow up, six were reported as “clinically well” and off antibiotic prophylaxis, according to Dr. Kohn, while the seventh patient was clinically well and receiving antimicrobial support.

Dr. Kohn is a scientific advisory board member for Orchard Therapeutics, which licensed the lentiviral gene therapy for X-CGD discussed in his presentation. He is also an inventor of intellectual property related to the therapy that UCLA has licensed to Orchard.

At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

SOURCE: Kohn DB et al. TCT 2019, Abstract LBA1.

HOUSTON – Lentiviral gene therapy appears safe and was potentially effective in a rare primary immunodeficiency disease known as X-linked chronic granulomatous disease, said Donald B. Kohn, MD, of the University of California, Los Angeles.

Seven of nine patients treated were “alive and well” at 12 months’ follow-up after receiving lentiviral vector transduced CD34+ cells, Dr. Kohn reported in a late-breaking clinical trial session at the Transplantation & Cellular Therapy Meetings.

Most patients were able to discontinue antibiotic prophylaxis for this disease, which is associated with severe, recurrent, and prolonged life-threatening infections, he said.

Results of the small study provide “proof of concept” for use of the gene therapy in the disease, though additional studies are needed to formally assess the clinical safety and efficacy of the approach, he said.

The estimated incidence of chronic granulomatous disease is 1 in 200,000 births in the United States, and the X-linked form is most common, occurring in about 60% of patients, Dr. Kohn told attendees of the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Most of these patients are treated with antibacterial or antifungal prophylaxis. While allogeneic hematopoietic stem cell transplantation is also an option, according to Dr. Kohn, the approach is limited by a lack of matched donors and graft-versus-host disease.

Dr. Kohn reported results for nine patients in the United States and the United Kingdom who were treated with the same G1XCGD lentiviral vector. The patients, who ranged in age from 2 to 27 years, underwent CD34+ cell mobilization or bone marrow isolation, transduction with the lentiviral vector, busulfan conditioning, and autologous transplantation.

All patients had confirmed X-linked chronic granulomatous disease, and had had at least one severe infection or inflammatory complication requiring hospitalization.

There were no infusion-related adverse events, and one serious adverse event, which was an inflammatory syndrome that resolved with steroids. Two patients died from complications unrelated to gene therapy, Dr. Kohn reported.

“The other patients are basically doing quite well,” he said.

Of the seven patients alive at the 12-month follow up, six were reported as “clinically well” and off antibiotic prophylaxis, according to Dr. Kohn, while the seventh patient was clinically well and receiving antimicrobial support.

Dr. Kohn is a scientific advisory board member for Orchard Therapeutics, which licensed the lentiviral gene therapy for X-CGD discussed in his presentation. He is also an inventor of intellectual property related to the therapy that UCLA has licensed to Orchard.

At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

SOURCE: Kohn DB et al. TCT 2019, Abstract LBA1.

HOUSTON – Allogeneic hematopoietic stem cell transplantation (allo-HCT) following a novel reduced-intensity conditioning regimen was largely successful in a heterogeneous cohort of 29 adults and children with primary immunodeficiency in a prospective clinical trial.

Sharon Worcester/MDedge News

At 1 year after transplant, overall survival was 98% and the estimated graft failure–free and graft-versus-host disease (GVHD)–free survival was 82% among the participants, who had various underlying primary immunodeficiencies (PIDs), Dimana Dimitrova, MD, reported at the Transplantation and Cellular Therapy Meetings.

GVHD-free survival was defined in this National Institutes of Health study as the absence of steroid-refractory grade 3-4 acute GVHD and chronic GVHD, noted Dr. Dimitrova of the NIH.

All patients, including 19 adults and 10 children (median age, 25 years), received a serotherapy-free, radiation-free, reduced-intensity conditioning regimen designed to optimize immune reconstitution, minimize toxicity and GVHD, reduce the risk of infectious complications, and enable successful use of alternative donors.

The conditioning platform included pentostatin on day –11 and day –7 at 4 mg/m² along with 8 days of low-dose cyclophosphamide and 2 days of pharmacokinetically dosed busulfan at 4,600 mmol/min. GVHD prophylaxis included posttransplantation cyclophosphamide, mycophenolate mofetil (MMF), and sirolimus.

All patients received T cell–replete bone marrow or peripheral blood stem cell allografts; 72% received alternative donor grafts, Dr. Dimitrova said.

Two patients died, including one with bacterial sepsis and invasive aspergillosis who died on day +44 and one with presumed viral encephalitis who died on day +110. The patients were high risk overall (median HCT–comorbidity index score of 3, with a range of 0-11), and the two who died had HCT-CI scores of 6 and 8, respectively.

An additional accidental death occurred at 18 months after transplant “in the setting of continued remission, good graft function, and no transplant-related complications,” she said.

Neutrophil recovery occurred at a median of 17 days after transplant; three patients experienced graft failure, including one primary failure with autologous recovery on day +14 and two secondary graft failures.

“Two patients with known underlying difficult-to-engraft diseases required second transplants using different nonmyeloabalative platforms, and nevertheless required donor lymphocyte infusions to avoid threatened secondary graft failure,” she said. “The third patient actually had sufficiently improved infectious disease control and has not needed a second transplant to date.”

Overall GVHD incidence using the novel platform has been extremely low, she said, noting that 14% of patients had grade 2-4 GVHD and 3% had grade 3-4 acute GVHD. There was no steroid-refractory GVHD or chronic GVHD.

Among the infectious complications, other than those that led to the two deaths, were cytomegalovirus reactivation in 7 of 16 patients at risk, BK virus–associated hemorrhagic cystitis in 19 of 22 patients at risk, and a suspected case of viral cardiomyopathy that ultimately resolved.

“Importantly, although many patients had Epstein-Barr virus [EBV] control issues prior to transplant, no patients received preemptive EBV-directed therapy, and no patients had EBV-PTLD [posttransplant lymphoproliferative disorder],” she said.

Additionally, blood stream infections were detected in five patients, there were two cases of confirmed aspergillosis, and one child developed cutaneous candidiasis. Other complications and toxicities appeared to relate to underlying pretransplant issues in the affected organ or exuberant immune responses to existing infection.

“Phenotype reversal was evident to some degree in all evaluable patients, even in those with mixed chimerism or unknown underlying genetic defect,” Dr. Dimitrova said.

All 10 patients with malignancy or lymphoproliferative disease as an additional indication for allo-HCT remain in remission, and most patients who required immunoglobulin replacement therapy prior to transplant have been able to discontinue it, she noted.

The findings of this study are of note, because while it has been known for decades that allo-HCT is a potentially curative therapy for patients with PIDs that arise from defects in cells of hematopoietic origin, it frequently fails because of complicating factors or is not an option, Dr. Dimitrova said.

“These patients will often enter transplant with multiple comorbidities and disease sequelae, particularly as diagnosis of PIDs increases in older children and adults following years of illness,” she explained, adding that related donor options may be limited if family members are also affected.

For this reason, and with the goal of improving access to allo-HCT to all who require it, the novel conditioning platform used in this study was developed.

The platform was well tolerated overall, Dr. Dimitrova said, emphasizing the “notably low” GVHD rates.

“Currently we are investigating reduced MMF with the goal of promoting earlier immune reconstitution, and a separate protocol has opened that includes several modifications to this platform aimed at patients with increased risk of graft failure who may not tolerate mixed chimerism early on,” she said, noting that both protocols are currently enrolling.

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Dimitrova reported having no financial disclosures.

[email protected]

SOURCE: Dimitrova D et al. TCT 2019, Abstract 54.

HOUSTON – Allogeneic hematopoietic stem cell transplantation (allo-HCT) following a novel reduced-intensity conditioning regimen was largely successful in a heterogeneous cohort of 29 adults and children with primary immunodeficiency in a prospective clinical trial.

Sharon Worcester/MDedge News

At 1 year after transplant, overall survival was 98% and the estimated graft failure–free and graft-versus-host disease (GVHD)–free survival was 82% among the participants, who had various underlying primary immunodeficiencies (PIDs), Dimana Dimitrova, MD, reported at the Transplantation and Cellular Therapy Meetings.

GVHD-free survival was defined in this National Institutes of Health study as the absence of steroid-refractory grade 3-4 acute GVHD and chronic GVHD, noted Dr. Dimitrova of the NIH.

All patients, including 19 adults and 10 children (median age, 25 years), received a serotherapy-free, radiation-free, reduced-intensity conditioning regimen designed to optimize immune reconstitution, minimize toxicity and GVHD, reduce the risk of infectious complications, and enable successful use of alternative donors.

The conditioning platform included pentostatin on day –11 and day –7 at 4 mg/m² along with 8 days of low-dose cyclophosphamide and 2 days of pharmacokinetically dosed busulfan at 4,600 mmol/min. GVHD prophylaxis included posttransplantation cyclophosphamide, mycophenolate mofetil (MMF), and sirolimus.

All patients received T cell–replete bone marrow or peripheral blood stem cell allografts; 72% received alternative donor grafts, Dr. Dimitrova said.

Two patients died, including one with bacterial sepsis and invasive aspergillosis who died on day +44 and one with presumed viral encephalitis who died on day +110. The patients were high risk overall (median HCT–comorbidity index score of 3, with a range of 0-11), and the two who died had HCT-CI scores of 6 and 8, respectively.

An additional accidental death occurred at 18 months after transplant “in the setting of continued remission, good graft function, and no transplant-related complications,” she said.

Neutrophil recovery occurred at a median of 17 days after transplant; three patients experienced graft failure, including one primary failure with autologous recovery on day +14 and two secondary graft failures.

“Two patients with known underlying difficult-to-engraft diseases required second transplants using different nonmyeloabalative platforms, and nevertheless required donor lymphocyte infusions to avoid threatened secondary graft failure,” she said. “The third patient actually had sufficiently improved infectious disease control and has not needed a second transplant to date.”

Overall GVHD incidence using the novel platform has been extremely low, she said, noting that 14% of patients had grade 2-4 GVHD and 3% had grade 3-4 acute GVHD. There was no steroid-refractory GVHD or chronic GVHD.

Among the infectious complications, other than those that led to the two deaths, were cytomegalovirus reactivation in 7 of 16 patients at risk, BK virus–associated hemorrhagic cystitis in 19 of 22 patients at risk, and a suspected case of viral cardiomyopathy that ultimately resolved.

“Importantly, although many patients had Epstein-Barr virus [EBV] control issues prior to transplant, no patients received preemptive EBV-directed therapy, and no patients had EBV-PTLD [posttransplant lymphoproliferative disorder],” she said.

Additionally, blood stream infections were detected in five patients, there were two cases of confirmed aspergillosis, and one child developed cutaneous candidiasis. Other complications and toxicities appeared to relate to underlying pretransplant issues in the affected organ or exuberant immune responses to existing infection.

“Phenotype reversal was evident to some degree in all evaluable patients, even in those with mixed chimerism or unknown underlying genetic defect,” Dr. Dimitrova said.

All 10 patients with malignancy or lymphoproliferative disease as an additional indication for allo-HCT remain in remission, and most patients who required immunoglobulin replacement therapy prior to transplant have been able to discontinue it, she noted.

The findings of this study are of note, because while it has been known for decades that allo-HCT is a potentially curative therapy for patients with PIDs that arise from defects in cells of hematopoietic origin, it frequently fails because of complicating factors or is not an option, Dr. Dimitrova said.

“These patients will often enter transplant with multiple comorbidities and disease sequelae, particularly as diagnosis of PIDs increases in older children and adults following years of illness,” she explained, adding that related donor options may be limited if family members are also affected.

For this reason, and with the goal of improving access to allo-HCT to all who require it, the novel conditioning platform used in this study was developed.

The platform was well tolerated overall, Dr. Dimitrova said, emphasizing the “notably low” GVHD rates.

“Currently we are investigating reduced MMF with the goal of promoting earlier immune reconstitution, and a separate protocol has opened that includes several modifications to this platform aimed at patients with increased risk of graft failure who may not tolerate mixed chimerism early on,” she said, noting that both protocols are currently enrolling.

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Dimitrova reported having no financial disclosures.

[email protected]

SOURCE: Dimitrova D et al. TCT 2019, Abstract 54.

HOUSTON – Allogeneic hematopoietic stem cell transplantation (allo-HCT) following a novel reduced-intensity conditioning regimen was largely successful in a heterogeneous cohort of 29 adults and children with primary immunodeficiency in a prospective clinical trial.

Sharon Worcester/MDedge News

At 1 year after transplant, overall survival was 98% and the estimated graft failure–free and graft-versus-host disease (GVHD)–free survival was 82% among the participants, who had various underlying primary immunodeficiencies (PIDs), Dimana Dimitrova, MD, reported at the Transplantation and Cellular Therapy Meetings.

GVHD-free survival was defined in this National Institutes of Health study as the absence of steroid-refractory grade 3-4 acute GVHD and chronic GVHD, noted Dr. Dimitrova of the NIH.

All patients, including 19 adults and 10 children (median age, 25 years), received a serotherapy-free, radiation-free, reduced-intensity conditioning regimen designed to optimize immune reconstitution, minimize toxicity and GVHD, reduce the risk of infectious complications, and enable successful use of alternative donors.

The conditioning platform included pentostatin on day –11 and day –7 at 4 mg/m² along with 8 days of low-dose cyclophosphamide and 2 days of pharmacokinetically dosed busulfan at 4,600 mmol/min. GVHD prophylaxis included posttransplantation cyclophosphamide, mycophenolate mofetil (MMF), and sirolimus.

All patients received T cell–replete bone marrow or peripheral blood stem cell allografts; 72% received alternative donor grafts, Dr. Dimitrova said.

Two patients died, including one with bacterial sepsis and invasive aspergillosis who died on day +44 and one with presumed viral encephalitis who died on day +110. The patients were high risk overall (median HCT–comorbidity index score of 3, with a range of 0-11), and the two who died had HCT-CI scores of 6 and 8, respectively.

An additional accidental death occurred at 18 months after transplant “in the setting of continued remission, good graft function, and no transplant-related complications,” she said.

Neutrophil recovery occurred at a median of 17 days after transplant; three patients experienced graft failure, including one primary failure with autologous recovery on day +14 and two secondary graft failures.

“Two patients with known underlying difficult-to-engraft diseases required second transplants using different nonmyeloabalative platforms, and nevertheless required donor lymphocyte infusions to avoid threatened secondary graft failure,” she said. “The third patient actually had sufficiently improved infectious disease control and has not needed a second transplant to date.”

Overall GVHD incidence using the novel platform has been extremely low, she said, noting that 14% of patients had grade 2-4 GVHD and 3% had grade 3-4 acute GVHD. There was no steroid-refractory GVHD or chronic GVHD.

Among the infectious complications, other than those that led to the two deaths, were cytomegalovirus reactivation in 7 of 16 patients at risk, BK virus–associated hemorrhagic cystitis in 19 of 22 patients at risk, and a suspected case of viral cardiomyopathy that ultimately resolved.

“Importantly, although many patients had Epstein-Barr virus [EBV] control issues prior to transplant, no patients received preemptive EBV-directed therapy, and no patients had EBV-PTLD [posttransplant lymphoproliferative disorder],” she said.

Additionally, blood stream infections were detected in five patients, there were two cases of confirmed aspergillosis, and one child developed cutaneous candidiasis. Other complications and toxicities appeared to relate to underlying pretransplant issues in the affected organ or exuberant immune responses to existing infection.

“Phenotype reversal was evident to some degree in all evaluable patients, even in those with mixed chimerism or unknown underlying genetic defect,” Dr. Dimitrova said.

All 10 patients with malignancy or lymphoproliferative disease as an additional indication for allo-HCT remain in remission, and most patients who required immunoglobulin replacement therapy prior to transplant have been able to discontinue it, she noted.

The findings of this study are of note, because while it has been known for decades that allo-HCT is a potentially curative therapy for patients with PIDs that arise from defects in cells of hematopoietic origin, it frequently fails because of complicating factors or is not an option, Dr. Dimitrova said.

“These patients will often enter transplant with multiple comorbidities and disease sequelae, particularly as diagnosis of PIDs increases in older children and adults following years of illness,” she explained, adding that related donor options may be limited if family members are also affected.

For this reason, and with the goal of improving access to allo-HCT to all who require it, the novel conditioning platform used in this study was developed.

The platform was well tolerated overall, Dr. Dimitrova said, emphasizing the “notably low” GVHD rates.

“Currently we are investigating reduced MMF with the goal of promoting earlier immune reconstitution, and a separate protocol has opened that includes several modifications to this platform aimed at patients with increased risk of graft failure who may not tolerate mixed chimerism early on,” she said, noting that both protocols are currently enrolling.

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Dimitrova reported having no financial disclosures.

[email protected]

SOURCE: Dimitrova D et al. TCT 2019, Abstract 54.

HOUSTON – Ixazomib may reduce treatment failure in patients with advanced chronic graft-versus-host disease (cGVHD), findings from a phase 2 trial suggest.

Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.

Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.

The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).

Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).

Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.

“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.

Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.

Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.

“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”

The overall response rate at 6 months was 40%. All 20 responders had partial responses.

The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).

Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.

The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.

The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.

Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.

There were five deaths, and two of them were considered possibly related to ixazomib.

“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.

[email protected]

SOURCE: Pidala J et al. TCT 2019, Abstract 35.

HOUSTON – Ixazomib may reduce treatment failure in patients with advanced chronic graft-versus-host disease (cGVHD), findings from a phase 2 trial suggest.

Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.

Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.

The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).

Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).

Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.

“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.

Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.

Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.

“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”

The overall response rate at 6 months was 40%. All 20 responders had partial responses.

The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).

Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.

The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.

The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.

Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.

There were five deaths, and two of them were considered possibly related to ixazomib.

“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.

[email protected]

SOURCE: Pidala J et al. TCT 2019, Abstract 35.

HOUSTON – Ixazomib may reduce treatment failure in patients with advanced chronic graft-versus-host disease (cGVHD), findings from a phase 2 trial suggest.

Patients who received ixazomib in this trial had a lower rate of treatment failure – a composite endpoint of death, relapse, and need for additional systemic immunosuppressive therapy – than that of historical controls.

Joseph Pidala, MD, PhD, of Moffitt Cancer Center in Tampa, Fla., presented this finding at the Transplantation & Cellular Therapy Meetings.

The trial (NCT02513498) included 50 patients with a median age of 58 years (range, 44-65). Patients had acute leukemia (52%), lymphoma (18%), chronic leukemia (12%), myelodysplastic syndromes/myeloproliferative neoplasms (8%), and myeloma (4%).

Most patients (90%) received peripheral blood transplants, but 10% received bone marrow. Patients had matched unrelated donors (48%), matched related donors (44%), mismatched unrelated donors (6%), and mismatched related donors (2%).

Most patients (84%) had severe cGVHD, but 16% had moderate cGVHD. About half of patients (52%) had four or more organs involved, and 78% received three or more prior lines of systemic therapy for cGVHD. The median time from cGVHD onset to trial enrollment was 33.5 months.

“[I]t was an advanced population that was highly treatment experienced,” Dr. Pidala said.

Initially, patients received ixazomib at 4 mg on days 1, 8, and 15 of a 28-day cycle for up to six cycles. However, the protocol was amended to allow additional cycles for responders.

Fifty-two percent of patients (n = 26) completed at least six cycles of therapy. The remaining patients stopped treatment because of unresolved toxicity, treatment failure, withdrawal, noncompliance, and death.

“Seven patients, in total, did continue therapy beyond six cycles,” Dr. Pidala said. “Six of these had partial response at 6 months, and one had stable disease.”

The overall response rate at 6 months was 40%. All 20 responders had partial responses.

The 6-month treatment failure rate was significantly lower in this trial than in historical controls (Blood 2013 121:2340-6). The rates of treatment failure were 28% and 44%, respectively (P = .01).

Treatment failure was largely due to the need for additional treatment, Dr. Pidala noted. Relapse and nonrelapse mortality were “uncommon” in this trial.

The investigators did not find any patient, transplant, or cGVHD-related factors significantly associated with 6-month treatment failure.

The failure-free survival rate at 6 months was 72% in this trial and 56% in historical controls. The failure-free survival rate at 12 months was 57% and 45%, respectively.

Serious adverse events occurred in 38% of patients on this trial. Patients required ixazomib dose reductions due to thrombocytopenia, fatigue, diarrhea, and infection.

There were five deaths, and two of them were considered possibly related to ixazomib.

“This was driven by the proximity of the death events to the last dose of ixazomib, specifically, within 1 month,” Dr. Pidala said. “One of these death events was a case of respiratory failure. The other was a case of sudden, unexplained death.”

The meeting was held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Pidala reported having nothing to disclose. Other investigators reported relationships with Pfizer, CSL Behring, Agios, Incyte, Genentech, and Takeda. The trial was sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute.

[email protected]

SOURCE: Pidala J et al. TCT 2019, Abstract 35.

HOUSTON — When given after transplant, azithromycin does not increase the risk of relapse in patients with moderate to severe chronic graft-versus-host disease (cGVHD) and bronchiolitis obliterans syndrome (BOS), according to a retrospective study.

A prior study, ALLOZITHRO (JAMA. 2017 Aug 8;318[6]:557-66), showed an increased risk of relapse and death in patients who received azithromycin as BOS prophylaxis prior to hematopoietic cell transplant (HCT).

That discovery prompted the Food and Drug Administration to release a safety communication warning prescribers about the risks associated with azithromycin as BOS prophylaxis. However, it wasn’t clear if the same risks exist when azithromycin is given for cGVHD management after HCT.

To gain some insight, Mark Shamoun, MD, of the University of Michigan, Ann Arbor, and his colleagues examined data on patients with moderate to severe cGVHD and BOS who received azithromycin after undergoing HCT to treat a hematologic malignancy.

Dr. Shamoun presented the group’s findings at the Transplantation & Cellular Therapy Meetings.

The researchers reviewed data on 239 patients enrolled in the University of Michigan’s HCT database from 2010 to 2017. The median age at baseline was 55 years (range, 4-72 years).

The patients received transplants to treat acute myeloid leukemia or myelodysplastic syndromes (n = 141), acute lymphoblastic leukemia (n = 40), lymphoma (n = 26), chronic leukemia (n = 24), multiple myeloma (n = 6), and myeloproliferative neoplasms (n = 2).

The patients had matched related donors (43%) or matched unrelated donors (57%). Most patients received peripheral blood transplants (84%), though some received bone marrow (14%) or cord blood (2%). All patients had moderate (38%) or severe (62%) cGVHD.

Patients were split into two cohorts. Patients in cohort A (n = 86) had BOS and received azithromycin for more than 14 days.

Patients in cohort B (n = 153) either did not receive azithromycin or received it for 14 days or less. Fewer than 5% of patients in cohort B had BOS.

Most other baseline characteristics were similar between the cohorts. However, severe cGVHD was more prevalent in cohort A than B — 78% and 51%, respectively.

In cohort A, the median time to the start of azithromycin was 15 months after HCT (range, 3-68 months). The median duration of azithromycin treatment was 26 months (range, 1-77 months).

Results

The 2-year relapse rate was significantly lower in patients who received azithromycin than in those who did not — 4% and 17%, respectively (P = .001).

There was a significant difference in relapse rate both from the time of HCT (P = .001) and from the start of azithromycin or cGVHD (P = .011).

There was no significant difference in overall survival between the cohorts, either from the time of HCT (P = .294) or from the start of azithromycin or cGVHD (P = .428).

Dr. Shamoun said these results suggest azithromycin does not increase the risk of relapse when it is used to manage cGVHD. However, this study is limited by its retrospective nature. In addition, most patients in cohort B did not have BOS, severe cGVHD was more common in cohort A, and the incidence of relapse was not calculated from the time of azithromycin initiation in both cohorts. Therefore, additional investigation is needed.

Dr. Shamoun presented these results at Transplantation & Cellular Therapy Meetings, which is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society, the American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Shamoun reported no conflicts of interest.

[email protected]

SOURCE: Shamoun M et al. TCT 2019, Abstract 33.

HOUSTON — When given after transplant, azithromycin does not increase the risk of relapse in patients with moderate to severe chronic graft-versus-host disease (cGVHD) and bronchiolitis obliterans syndrome (BOS), according to a retrospective study.

A prior study, ALLOZITHRO (JAMA. 2017 Aug 8;318[6]:557-66), showed an increased risk of relapse and death in patients who received azithromycin as BOS prophylaxis prior to hematopoietic cell transplant (HCT).

That discovery prompted the Food and Drug Administration to release a safety communication warning prescribers about the risks associated with azithromycin as BOS prophylaxis. However, it wasn’t clear if the same risks exist when azithromycin is given for cGVHD management after HCT.

To gain some insight, Mark Shamoun, MD, of the University of Michigan, Ann Arbor, and his colleagues examined data on patients with moderate to severe cGVHD and BOS who received azithromycin after undergoing HCT to treat a hematologic malignancy.

Dr. Shamoun presented the group’s findings at the Transplantation & Cellular Therapy Meetings.

The researchers reviewed data on 239 patients enrolled in the University of Michigan’s HCT database from 2010 to 2017. The median age at baseline was 55 years (range, 4-72 years).

The patients received transplants to treat acute myeloid leukemia or myelodysplastic syndromes (n = 141), acute lymphoblastic leukemia (n = 40), lymphoma (n = 26), chronic leukemia (n = 24), multiple myeloma (n = 6), and myeloproliferative neoplasms (n = 2).

The patients had matched related donors (43%) or matched unrelated donors (57%). Most patients received peripheral blood transplants (84%), though some received bone marrow (14%) or cord blood (2%). All patients had moderate (38%) or severe (62%) cGVHD.

Patients were split into two cohorts. Patients in cohort A (n = 86) had BOS and received azithromycin for more than 14 days.

Patients in cohort B (n = 153) either did not receive azithromycin or received it for 14 days or less. Fewer than 5% of patients in cohort B had BOS.

Most other baseline characteristics were similar between the cohorts. However, severe cGVHD was more prevalent in cohort A than B — 78% and 51%, respectively.

In cohort A, the median time to the start of azithromycin was 15 months after HCT (range, 3-68 months). The median duration of azithromycin treatment was 26 months (range, 1-77 months).

Results

The 2-year relapse rate was significantly lower in patients who received azithromycin than in those who did not — 4% and 17%, respectively (P = .001).

There was a significant difference in relapse rate both from the time of HCT (P = .001) and from the start of azithromycin or cGVHD (P = .011).

There was no significant difference in overall survival between the cohorts, either from the time of HCT (P = .294) or from the start of azithromycin or cGVHD (P = .428).

Dr. Shamoun said these results suggest azithromycin does not increase the risk of relapse when it is used to manage cGVHD. However, this study is limited by its retrospective nature. In addition, most patients in cohort B did not have BOS, severe cGVHD was more common in cohort A, and the incidence of relapse was not calculated from the time of azithromycin initiation in both cohorts. Therefore, additional investigation is needed.

Dr. Shamoun presented these results at Transplantation & Cellular Therapy Meetings, which is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society, the American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Shamoun reported no conflicts of interest.

[email protected]

SOURCE: Shamoun M et al. TCT 2019, Abstract 33.

HOUSTON — When given after transplant, azithromycin does not increase the risk of relapse in patients with moderate to severe chronic graft-versus-host disease (cGVHD) and bronchiolitis obliterans syndrome (BOS), according to a retrospective study.

A prior study, ALLOZITHRO (JAMA. 2017 Aug 8;318[6]:557-66), showed an increased risk of relapse and death in patients who received azithromycin as BOS prophylaxis prior to hematopoietic cell transplant (HCT).

That discovery prompted the Food and Drug Administration to release a safety communication warning prescribers about the risks associated with azithromycin as BOS prophylaxis. However, it wasn’t clear if the same risks exist when azithromycin is given for cGVHD management after HCT.

To gain some insight, Mark Shamoun, MD, of the University of Michigan, Ann Arbor, and his colleagues examined data on patients with moderate to severe cGVHD and BOS who received azithromycin after undergoing HCT to treat a hematologic malignancy.

Dr. Shamoun presented the group’s findings at the Transplantation & Cellular Therapy Meetings.

The researchers reviewed data on 239 patients enrolled in the University of Michigan’s HCT database from 2010 to 2017. The median age at baseline was 55 years (range, 4-72 years).

The patients received transplants to treat acute myeloid leukemia or myelodysplastic syndromes (n = 141), acute lymphoblastic leukemia (n = 40), lymphoma (n = 26), chronic leukemia (n = 24), multiple myeloma (n = 6), and myeloproliferative neoplasms (n = 2).

The patients had matched related donors (43%) or matched unrelated donors (57%). Most patients received peripheral blood transplants (84%), though some received bone marrow (14%) or cord blood (2%). All patients had moderate (38%) or severe (62%) cGVHD.

Patients were split into two cohorts. Patients in cohort A (n = 86) had BOS and received azithromycin for more than 14 days.

Patients in cohort B (n = 153) either did not receive azithromycin or received it for 14 days or less. Fewer than 5% of patients in cohort B had BOS.

Most other baseline characteristics were similar between the cohorts. However, severe cGVHD was more prevalent in cohort A than B — 78% and 51%, respectively.

In cohort A, the median time to the start of azithromycin was 15 months after HCT (range, 3-68 months). The median duration of azithromycin treatment was 26 months (range, 1-77 months).

Results

The 2-year relapse rate was significantly lower in patients who received azithromycin than in those who did not — 4% and 17%, respectively (P = .001).

There was a significant difference in relapse rate both from the time of HCT (P = .001) and from the start of azithromycin or cGVHD (P = .011).

There was no significant difference in overall survival between the cohorts, either from the time of HCT (P = .294) or from the start of azithromycin or cGVHD (P = .428).

Dr. Shamoun said these results suggest azithromycin does not increase the risk of relapse when it is used to manage cGVHD. However, this study is limited by its retrospective nature. In addition, most patients in cohort B did not have BOS, severe cGVHD was more common in cohort A, and the incidence of relapse was not calculated from the time of azithromycin initiation in both cohorts. Therefore, additional investigation is needed.

Dr. Shamoun presented these results at Transplantation & Cellular Therapy Meetings, which is held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At the meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society, the American Society for Transplantation and Cellular Therapy (ASTCT).

Dr. Shamoun reported no conflicts of interest.

[email protected]

SOURCE: Shamoun M et al. TCT 2019, Abstract 33.

Previously unknown risk factors for secondary skin cancer linked with allogeneic hematopoietic cell transplantation (HCT) have been identified, researchers report after a retrospective analysis.

“We confirmed [graft-versus-host disease] as a risk factor, identified [chronic lymphocytic leukemia] as an additional risk factor, and found that patients who received myeloablative transplants in adulthood had fewer [basal cell carcinomas] than their counterparts,” Peggy A. Wu, MD, of the Beth Israel Deaconess Medical Center in Boston, and her colleagues wrote in the Journal of Investigative Dermatology.

The team analyzed 1,974 patients who underwent transplantation for various types of hematologic cancer and survived for a minimum of 100 days following transplant. Among this cohort, 119 patients developed various forms of skin cancer, including basal and squamous cell carcinoma.

Reports of skin malignancy were confirmed using physician records and pathology reports. Dr. Wu and her colleagues excluded patients whose indication for transplant was a primary immunodeficiency or Fanconi anemia.

“Reflecting advances that allow older patients to be eligible for HCT, the median age at transplantation of our cohort was one of the oldest (51.1 years) in the literature,” the researchers wrote.

In univariable models, the researchers found that prior chronic lymphocytic leukemia (CLL) (hazard ratio, 2.2; 95% CI, 1.3-3.7), chronic graft-versus-host disease (GVHD) (HR, 3.1; 95% CI, 1.7-5.4), and age at transplant of more than 60 years (HR, 10.8; 95% CI, 3.3-35.6) were all linked to an increased risk for squamous cell carcinomas. A multivariable analysis found that these factors continued as significant risk factors.

For basal cell carcinomas, the risk factors identified were prior CLL (HR, 3.5; 95% CI, 2.0-6.4), acute GVHD (HR, 1.9; 95% CI, 1.1-3.3), and chronic GVHD (HR, 3.2; 95% CI, 1.6-6.5) using univariable models. These factors all continued to be significant in multivariable analysis.

Additionally, the researchers found that a myeloablative conditioning regimen and total body irradiation were protective against development of basal cell carcinomas in univariable models. However, the protective effect continued for myeloablative condition in the multivariable model only.

“To our knowledge, previously unreported risk factors in this contemporary cohort include prior CLL for squamous cell carcinoma and basal cell carcinoma and reduced-intensity conditioning for basal cell carcinoma,” the researchers wrote.

The study was supported by the Skin Cancer Foundation, Women’s Dermatologic Society, Harvard Catalyst, and Harvard University. The authors reported having no conflicts of interest.
 

SOURCE: Wu PA et al. J Invest Dermatol. 2019 Mar;139(3):591-9.

Previously unknown risk factors for secondary skin cancer linked with allogeneic hematopoietic cell transplantation (HCT) have been identified, researchers report after a retrospective analysis.

“We confirmed [graft-versus-host disease] as a risk factor, identified [chronic lymphocytic leukemia] as an additional risk factor, and found that patients who received myeloablative transplants in adulthood had fewer [basal cell carcinomas] than their counterparts,” Peggy A. Wu, MD, of the Beth Israel Deaconess Medical Center in Boston, and her colleagues wrote in the Journal of Investigative Dermatology.

The team analyzed 1,974 patients who underwent transplantation for various types of hematologic cancer and survived for a minimum of 100 days following transplant. Among this cohort, 119 patients developed various forms of skin cancer, including basal and squamous cell carcinoma.

Reports of skin malignancy were confirmed using physician records and pathology reports. Dr. Wu and her colleagues excluded patients whose indication for transplant was a primary immunodeficiency or Fanconi anemia.

“Reflecting advances that allow older patients to be eligible for HCT, the median age at transplantation of our cohort was one of the oldest (51.1 years) in the literature,” the researchers wrote.

In univariable models, the researchers found that prior chronic lymphocytic leukemia (CLL) (hazard ratio, 2.2; 95% CI, 1.3-3.7), chronic graft-versus-host disease (GVHD) (HR, 3.1; 95% CI, 1.7-5.4), and age at transplant of more than 60 years (HR, 10.8; 95% CI, 3.3-35.6) were all linked to an increased risk for squamous cell carcinomas. A multivariable analysis found that these factors continued as significant risk factors.

For basal cell carcinomas, the risk factors identified were prior CLL (HR, 3.5; 95% CI, 2.0-6.4), acute GVHD (HR, 1.9; 95% CI, 1.1-3.3), and chronic GVHD (HR, 3.2; 95% CI, 1.6-6.5) using univariable models. These factors all continued to be significant in multivariable analysis.

Additionally, the researchers found that a myeloablative conditioning regimen and total body irradiation were protective against development of basal cell carcinomas in univariable models. However, the protective effect continued for myeloablative condition in the multivariable model only.

“To our knowledge, previously unreported risk factors in this contemporary cohort include prior CLL for squamous cell carcinoma and basal cell carcinoma and reduced-intensity conditioning for basal cell carcinoma,” the researchers wrote.

The study was supported by the Skin Cancer Foundation, Women’s Dermatologic Society, Harvard Catalyst, and Harvard University. The authors reported having no conflicts of interest.
 

SOURCE: Wu PA et al. J Invest Dermatol. 2019 Mar;139(3):591-9.

Previously unknown risk factors for secondary skin cancer linked with allogeneic hematopoietic cell transplantation (HCT) have been identified, researchers report after a retrospective analysis.

“We confirmed [graft-versus-host disease] as a risk factor, identified [chronic lymphocytic leukemia] as an additional risk factor, and found that patients who received myeloablative transplants in adulthood had fewer [basal cell carcinomas] than their counterparts,” Peggy A. Wu, MD, of the Beth Israel Deaconess Medical Center in Boston, and her colleagues wrote in the Journal of Investigative Dermatology.

The team analyzed 1,974 patients who underwent transplantation for various types of hematologic cancer and survived for a minimum of 100 days following transplant. Among this cohort, 119 patients developed various forms of skin cancer, including basal and squamous cell carcinoma.

Reports of skin malignancy were confirmed using physician records and pathology reports. Dr. Wu and her colleagues excluded patients whose indication for transplant was a primary immunodeficiency or Fanconi anemia.

“Reflecting advances that allow older patients to be eligible for HCT, the median age at transplantation of our cohort was one of the oldest (51.1 years) in the literature,” the researchers wrote.

In univariable models, the researchers found that prior chronic lymphocytic leukemia (CLL) (hazard ratio, 2.2; 95% CI, 1.3-3.7), chronic graft-versus-host disease (GVHD) (HR, 3.1; 95% CI, 1.7-5.4), and age at transplant of more than 60 years (HR, 10.8; 95% CI, 3.3-35.6) were all linked to an increased risk for squamous cell carcinomas. A multivariable analysis found that these factors continued as significant risk factors.

For basal cell carcinomas, the risk factors identified were prior CLL (HR, 3.5; 95% CI, 2.0-6.4), acute GVHD (HR, 1.9; 95% CI, 1.1-3.3), and chronic GVHD (HR, 3.2; 95% CI, 1.6-6.5) using univariable models. These factors all continued to be significant in multivariable analysis.

Additionally, the researchers found that a myeloablative conditioning regimen and total body irradiation were protective against development of basal cell carcinomas in univariable models. However, the protective effect continued for myeloablative condition in the multivariable model only.

“To our knowledge, previously unreported risk factors in this contemporary cohort include prior CLL for squamous cell carcinoma and basal cell carcinoma and reduced-intensity conditioning for basal cell carcinoma,” the researchers wrote.

The study was supported by the Skin Cancer Foundation, Women’s Dermatologic Society, Harvard Catalyst, and Harvard University. The authors reported having no conflicts of interest.
 

SOURCE: Wu PA et al. J Invest Dermatol. 2019 Mar;139(3):591-9.

HOUSTON – Midostaurin maintenance therapy along with standard-of-care treatment after allogeneic stem cell transplant (alloSCT) in patients with acute myeloid leukemia (AML) appears to reduce the risk of relapse, according to findings from the randomized, phase 2 RADIUS trial.

Sharon Worcester/MDedge News

Notably, the effect of midostaurin in this open-label, exploratory trial was most pronounced in patients with high levels of phosphorylated FLT3 (pFLT3) inhibition as assessed by plasma inhibitor activity assay, Richard T. Maziarz, MD, reported at the Transplantation & Cellular Therapy Meetings.

“The median [pFLT3 reduction] was less than 70% ... those patients who had the deepest level inhibition maintained the highest likelihood of staying free of disease,” Dr. Maziarz, a professor of medicine at Oregon Health & Science University, Portland, said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).


Midostaurin is a multitargeted tyrosine kinase inhibitor (TKI) that was shown in the pivotal RATIFY trial to significantly improve event-free and overall survival versus placebo when interspersed with induction and consolidation chemotherapy and also when used for maintenance in adults with newly diagnosed FLT3-mutated AML, Dr. Maziarz explained. He noted that patients in the RATIFY study who underwent alloSCT did not receive midostaurin maintenance (N Engl J Med. 2017; 377:454-64).

Although alloSCT provides the greatest likelihood of sustained remission in AML, relapse rates remain high at 30%-59%, he said, adding that, “in the setting of transplantation, FLT3 expression, or FLT3-ITD [internal tandem duplication] ... is a poor risk feature.”

[email protected]

HOUSTON – Midostaurin maintenance therapy along with standard-of-care treatment after allogeneic stem cell transplant (alloSCT) in patients with acute myeloid leukemia (AML) appears to reduce the risk of relapse, according to findings from the randomized, phase 2 RADIUS trial.

Sharon Worcester/MDedge News

Notably, the effect of midostaurin in this open-label, exploratory trial was most pronounced in patients with high levels of phosphorylated FLT3 (pFLT3) inhibition as assessed by plasma inhibitor activity assay, Richard T. Maziarz, MD, reported at the Transplantation & Cellular Therapy Meetings.

“The median [pFLT3 reduction] was less than 70% ... those patients who had the deepest level inhibition maintained the highest likelihood of staying free of disease,” Dr. Maziarz, a professor of medicine at Oregon Health & Science University, Portland, said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).


Midostaurin is a multitargeted tyrosine kinase inhibitor (TKI) that was shown in the pivotal RATIFY trial to significantly improve event-free and overall survival versus placebo when interspersed with induction and consolidation chemotherapy and also when used for maintenance in adults with newly diagnosed FLT3-mutated AML, Dr. Maziarz explained. He noted that patients in the RATIFY study who underwent alloSCT did not receive midostaurin maintenance (N Engl J Med. 2017; 377:454-64).

Although alloSCT provides the greatest likelihood of sustained remission in AML, relapse rates remain high at 30%-59%, he said, adding that, “in the setting of transplantation, FLT3 expression, or FLT3-ITD [internal tandem duplication] ... is a poor risk feature.”

[email protected]

HOUSTON – Midostaurin maintenance therapy along with standard-of-care treatment after allogeneic stem cell transplant (alloSCT) in patients with acute myeloid leukemia (AML) appears to reduce the risk of relapse, according to findings from the randomized, phase 2 RADIUS trial.

Sharon Worcester/MDedge News

Notably, the effect of midostaurin in this open-label, exploratory trial was most pronounced in patients with high levels of phosphorylated FLT3 (pFLT3) inhibition as assessed by plasma inhibitor activity assay, Richard T. Maziarz, MD, reported at the Transplantation & Cellular Therapy Meetings.

“The median [pFLT3 reduction] was less than 70% ... those patients who had the deepest level inhibition maintained the highest likelihood of staying free of disease,” Dr. Maziarz, a professor of medicine at Oregon Health & Science University, Portland, said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).


Midostaurin is a multitargeted tyrosine kinase inhibitor (TKI) that was shown in the pivotal RATIFY trial to significantly improve event-free and overall survival versus placebo when interspersed with induction and consolidation chemotherapy and also when used for maintenance in adults with newly diagnosed FLT3-mutated AML, Dr. Maziarz explained. He noted that patients in the RATIFY study who underwent alloSCT did not receive midostaurin maintenance (N Engl J Med. 2017; 377:454-64).

Although alloSCT provides the greatest likelihood of sustained remission in AML, relapse rates remain high at 30%-59%, he said, adding that, “in the setting of transplantation, FLT3 expression, or FLT3-ITD [internal tandem duplication] ... is a poor risk feature.”

[email protected]

HOUSTON – With a median follow-up now exceeding 2 years, 39% of refractory large B-cell lymphoma patients enrolled in the pivotal ZUMA-1 trial have maintained ongoing response to axicabtagene ciloleucel, according to an investigator involved in the study.

Mary Jo M. Dales/MDedge News

SOURCE: Neelapu SS et al. TCT 2019, Abstract 82.

HOUSTON – With a median follow-up now exceeding 2 years, 39% of refractory large B-cell lymphoma patients enrolled in the pivotal ZUMA-1 trial have maintained ongoing response to axicabtagene ciloleucel, according to an investigator involved in the study.

Mary Jo M. Dales/MDedge News

SOURCE: Neelapu SS et al. TCT 2019, Abstract 82.

HOUSTON – With a median follow-up now exceeding 2 years, 39% of refractory large B-cell lymphoma patients enrolled in the pivotal ZUMA-1 trial have maintained ongoing response to axicabtagene ciloleucel, according to an investigator involved in the study.

Mary Jo M. Dales/MDedge News

SOURCE: Neelapu SS et al. TCT 2019, Abstract 82.

HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.

Andrew D. Bowser/MDedge News

“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.

“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.

There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.

Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 10⁶ cells/kg, 5 remain in ongoing complete remission.

SOURCE: Shah NN et al. TCT 2019, Abstract 80.

HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.

Andrew D. Bowser/MDedge News

“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.

“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.

There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.

Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 10⁶ cells/kg, 5 remain in ongoing complete remission.

SOURCE: Shah NN et al. TCT 2019, Abstract 80.

HOUSTON – A dual-targeted, locally manufactured, anti-CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy was safe and produced ongoing complete responses in a phase 1 study of heavily pretreated non-Hodgkin lymphoma patients, an investigator reported.

Andrew D. Bowser/MDedge News

“So far, this trial has demonstrated safety for this bispecific vector and suggests a clinical signal, with 7 out of 12 patients with ongoing CR, and with minimal toxicity,” Dr. Hari said at the Transplantation & Cellular Therapy Meetings.

“Point of care delivery, we think, allowed patients to have fresh infusion of CAR T cells, with the avoidance of cryopreservation,” added Dr. Hari, who presented the results on behalf of coinvestigators at the Medical College of Wisconsin and Lentigen Technology.

There was no grade 3 or 4 neurotoxicity or cytokine release syndrome among the 12 patients reported to date in the phase 1, dose-escalation trial, and no patient required intensive care, according to Dr. Hari. Grade 1 and 2 neurotoxicity occurred in two and one patients, respectively, while grade 1 and 2 cytokine release syndrome was observed in three patients each.

Among the 12 patients treated to date, the overall response rate was 81% at day 28, Dr. Hari said, noting that of 6 patients treated at the goal dose of 2.5 x 10⁶ cells/kg, 5 remain in ongoing complete remission.

SOURCE: Shah NN et al. TCT 2019, Abstract 80.

HOUSTON – Allogeneic blood and marrow transplantation (alloBMT) with posttransplant cyclophosphamide (PTCy) is relatively safe and feasible in septuagenarians with hematologic malignancies and should be considered in this population, findings from a review of 108 cases suggest.

Sharon Worcester/MDedge News

The main difference in outcomes in older versus younger patients is a higher – but still low – rate of nonrelapse mortality (NRM) that appears to be due in part to age-related causes, Philip Hollingsworth Imus, MD, of Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, reported at the Transplantation & Cellular Therapy Meetings.

Overall survival (OS) among the 108 consecutive patients over age 70 years who underwent alloBMT at Johns Hopkins from Jan. 1, 2009, through March 31, 2018, was 64% at 1 year and 43% at 3 years, and progression-free survival (PFS) was 50% at 1 year and 32% at 3 years, Dr. Imus said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

NRM, especially later NRM, however, seemed to be increased, he said, noting that 6-month NRM was acceptable at 14%, but at 1 and 3 years it was 20% and 29%, respectively.

“In contrast to younger patients, [hematopoietic cell transplantation–specific comorbidity index] did not seem to predict NRM in our cohort,” he said.

Early causes of NRM were “in keeping with what we typically see,” and included pneumonia, sepsis, and a few cases of cytokine release syndrome, but later causes of NRM included some that are commonly seen in older patients without hematologic malignancies, such as secondary malignancies, dementia, falls, and cerebrovascular accidents, he said.

[email protected]

SOURCE: Imus P et al. TCT 2019, Abstract 42.

HOUSTON – Allogeneic blood and marrow transplantation (alloBMT) with posttransplant cyclophosphamide (PTCy) is relatively safe and feasible in septuagenarians with hematologic malignancies and should be considered in this population, findings from a review of 108 cases suggest.

Sharon Worcester/MDedge News

The main difference in outcomes in older versus younger patients is a higher – but still low – rate of nonrelapse mortality (NRM) that appears to be due in part to age-related causes, Philip Hollingsworth Imus, MD, of Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, reported at the Transplantation & Cellular Therapy Meetings.

Overall survival (OS) among the 108 consecutive patients over age 70 years who underwent alloBMT at Johns Hopkins from Jan. 1, 2009, through March 31, 2018, was 64% at 1 year and 43% at 3 years, and progression-free survival (PFS) was 50% at 1 year and 32% at 3 years, Dr. Imus said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

NRM, especially later NRM, however, seemed to be increased, he said, noting that 6-month NRM was acceptable at 14%, but at 1 and 3 years it was 20% and 29%, respectively.

“In contrast to younger patients, [hematopoietic cell transplantation–specific comorbidity index] did not seem to predict NRM in our cohort,” he said.

Early causes of NRM were “in keeping with what we typically see,” and included pneumonia, sepsis, and a few cases of cytokine release syndrome, but later causes of NRM included some that are commonly seen in older patients without hematologic malignancies, such as secondary malignancies, dementia, falls, and cerebrovascular accidents, he said.

[email protected]

SOURCE: Imus P et al. TCT 2019, Abstract 42.

HOUSTON – Allogeneic blood and marrow transplantation (alloBMT) with posttransplant cyclophosphamide (PTCy) is relatively safe and feasible in septuagenarians with hematologic malignancies and should be considered in this population, findings from a review of 108 cases suggest.

Sharon Worcester/MDedge News

The main difference in outcomes in older versus younger patients is a higher – but still low – rate of nonrelapse mortality (NRM) that appears to be due in part to age-related causes, Philip Hollingsworth Imus, MD, of Johns Hopkins University and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, reported at the Transplantation & Cellular Therapy Meetings.

Overall survival (OS) among the 108 consecutive patients over age 70 years who underwent alloBMT at Johns Hopkins from Jan. 1, 2009, through March 31, 2018, was 64% at 1 year and 43% at 3 years, and progression-free survival (PFS) was 50% at 1 year and 32% at 3 years, Dr. Imus said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).

NRM, especially later NRM, however, seemed to be increased, he said, noting that 6-month NRM was acceptable at 14%, but at 1 and 3 years it was 20% and 29%, respectively.

“In contrast to younger patients, [hematopoietic cell transplantation–specific comorbidity index] did not seem to predict NRM in our cohort,” he said.

Early causes of NRM were “in keeping with what we typically see,” and included pneumonia, sepsis, and a few cases of cytokine release syndrome, but later causes of NRM included some that are commonly seen in older patients without hematologic malignancies, such as secondary malignancies, dementia, falls, and cerebrovascular accidents, he said.

[email protected]

SOURCE: Imus P et al. TCT 2019, Abstract 42.

HOUSTON – Minimal residual disease (MRD) negativity by multiparameter flow cytometry was linked to survival benefit in multiple myeloma patients undergoing autologous transplantation, according to results of the first U.S.-based study evaluating this endpoint as part of a national randomized clinical trial.

Andrew D. Bowser/MDedge News

MRD-negative status was prognostic for improved progression-free survival at all time points measured over the course of 1 year post transplant, in this ancillary study of patients in the randomized, 3-arm STAMiNA trial.

Moreover, there was an overall survival benefit for MRD-negative status at 1 year post transplant, investigator Theresa A. Hahn, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., reported at the Transplantation & Cellular Therapy Meetings.

There was no significant difference in rate of conversion to MRD negativity in the arms of the trial, which evaluated several different upfront approaches to autologous hematopoietic stem cell transplantation (HCT).

Assessments of MRD beyond 1 year post transplant may be valuable in future trials, Dr. Hahn said.

“Trials are needed incorporating MRD as an endpoint for treatment decisions to augment, change, or discontinue therapy,” she added.

Results of the ancillary study known as PRIMeR (Prognostic Immunophenotyping for Myeloma Response) included 445 patients from STAMiNA who underwent MRD assessment at baseline, prior to maintenance, and at 1 year post transplantation.

SOURCE: Hahn TE et al. TCT 2019, Abstract 6.

HOUSTON – Minimal residual disease (MRD) negativity by multiparameter flow cytometry was linked to survival benefit in multiple myeloma patients undergoing autologous transplantation, according to results of the first U.S.-based study evaluating this endpoint as part of a national randomized clinical trial.

Andrew D. Bowser/MDedge News

MRD-negative status was prognostic for improved progression-free survival at all time points measured over the course of 1 year post transplant, in this ancillary study of patients in the randomized, 3-arm STAMiNA trial.

Moreover, there was an overall survival benefit for MRD-negative status at 1 year post transplant, investigator Theresa A. Hahn, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., reported at the Transplantation & Cellular Therapy Meetings.

There was no significant difference in rate of conversion to MRD negativity in the arms of the trial, which evaluated several different upfront approaches to autologous hematopoietic stem cell transplantation (HCT).

Assessments of MRD beyond 1 year post transplant may be valuable in future trials, Dr. Hahn said.

“Trials are needed incorporating MRD as an endpoint for treatment decisions to augment, change, or discontinue therapy,” she added.

Results of the ancillary study known as PRIMeR (Prognostic Immunophenotyping for Myeloma Response) included 445 patients from STAMiNA who underwent MRD assessment at baseline, prior to maintenance, and at 1 year post transplantation.

SOURCE: Hahn TE et al. TCT 2019, Abstract 6.

HOUSTON – Minimal residual disease (MRD) negativity by multiparameter flow cytometry was linked to survival benefit in multiple myeloma patients undergoing autologous transplantation, according to results of the first U.S.-based study evaluating this endpoint as part of a national randomized clinical trial.

Andrew D. Bowser/MDedge News

MRD-negative status was prognostic for improved progression-free survival at all time points measured over the course of 1 year post transplant, in this ancillary study of patients in the randomized, 3-arm STAMiNA trial.

Moreover, there was an overall survival benefit for MRD-negative status at 1 year post transplant, investigator Theresa A. Hahn, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., reported at the Transplantation & Cellular Therapy Meetings.

There was no significant difference in rate of conversion to MRD negativity in the arms of the trial, which evaluated several different upfront approaches to autologous hematopoietic stem cell transplantation (HCT).

Assessments of MRD beyond 1 year post transplant may be valuable in future trials, Dr. Hahn said.

“Trials are needed incorporating MRD as an endpoint for treatment decisions to augment, change, or discontinue therapy,” she added.

Results of the ancillary study known as PRIMeR (Prognostic Immunophenotyping for Myeloma Response) included 445 patients from STAMiNA who underwent MRD assessment at baseline, prior to maintenance, and at 1 year post transplantation.

SOURCE: Hahn TE et al. TCT 2019, Abstract 6.