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KTE-X19 produces highest response rate in MCL subgroup
ORLANDO – KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated unprecedented efficacy in the ZUMA-2 trial, according to an investigator involved in the study.
KTE-X19 produced a 93% overall response rate in patients with relapsed/refractory mantle cell lymphoma (MCL). This is the highest reported response rate in patients who have failed treatment with a Bruton’s tyrosine kinase (BTK) inhibitor, said Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr. Wang presented results from ZUMA-2 at the annual meeting of the American Society of Hematology.
“Patients with relapsed/refractory MCL have very poor outcomes,” Dr. Wang noted. “In patients who progress after BTK inhibition therapy, the overall response rate is only between 25% and 42%, and the overall survival is only between 6 and 10 months. Few patients proceed to allogeneic transplantation.”
The phase 2 ZUMA-2 trial was designed to test KTE-X19 in these patients. KTE-X19 is an anti-CD19 CAR T-cell therapy containing a CD3-zeta T-cell activation domain and a CD28 signaling domain. KTE-X19 is distinct from axicabtagene ciloleucel (KTE-C19) because the manufacturing process for KTE-X19 removes circulating tumor cells.
The trial enrolled 74 patients, and 68 of them received KTE-X19. Manufacturing failed for three patients, two patients died of progressive disease before they could receive KTE-X19, and one patient was found to be ineligible for treatment.
The 68 patients had a median age of 65 years (range, 38-79 years), and 84% were men. A majority of patients (85%) had stage IV disease and classical (59%) or blastoid (25%) morphology. Most patients (69%) had a Ki-67 proliferation index of 50% or greater, and most (56%) were intermediate- or high-risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI).
Patients had received a median of three prior therapies (range, one to five). All had been treated with a BTK inhibitor, with 85% receiving ibrutinib, 24% receiving acalabrutinib, and 9% receiving both. Most patients (68%) were refractory to BTK inhibition, and 32% relapsed on or after BTK inhibitor therapy.
In this study, patients could receive bridging therapy to keep their disease stable while KTE-X19 was being manufactured. There were 25 patients who received bridging therapy, which consisted of ibrutinib (n = 14), acalabrutinib (n = 5), dexamethasone (n = 12), and/or methylprednisolone (n = 2). Six patients received both BTK inhibitors and steroids.
All patients received conditioning with fludarabine and cyclophosphamide, followed by a single infusion of KTE-X19 at 2x106.
Efficacy
Sixty patients were evaluable for efficacy, and the median follow-up was 12.3 months (range, 7.0-32.3 months).
The overall response rate was 93%, with 67% of patients achieving a complete response and 27% achieving a partial response. Three percent of patients had stable disease, and 3% had progressive disease.
“The overall response rate was consistent across key subgroups, without any statistical difference,” Dr. Wang said. “This includes Ki-67, MIPI, and prior use of either steroids or bridging therapy.”
The median time to response was 1.0 month, and the median time to complete response was 3.0 months. Responses deepened over time, with 35% of patients converting from a partial response to a complete response, and 5% converting from stable disease to complete response.
The median duration of response has not been reached. At last follow-up, 57% of all patients and 78% of complete responders were still in response.
The median progression-free and overall survival have not been reached. At 12 months, the progression-free survival rate was 61%, and the overall survival rate was 83%.
Safety
All 68 patients were evaluable for safety. The most common adverse events were pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypotension (51%).
Grade 3/4 adverse events included pyrexia (13%), neutropenia (85%), thrombocytopenia (51%), anemia (50%), hypotension (22%), hypoxia (21%), hypophosphatemia (22%), fatigue (1%), and headache (1%).
There were two grade 5 treatment-related adverse events – organizing pneumonia on day 37 and staphylococcal bacteremia on day 134.
Cytokine release syndrome (CRS) occurred in 91% of patients, with 15% experiencing grade 3 or higher CRS. Patients were treated with tocilizumab or corticosteroids, and all CRS events resolved.
Neurologic adverse events occurred in 63% of patients, with grade 3 or higher events occurring in 31%. Neurologic events were treated with tocilizumab or corticosteroids, and 86% of neurologic events resolved.
This trial was sponsored by Kite, a Gilead company. Dr. Wang reported financial relationships with Kite and other companies.
SOURCE: Wang M et al. ASH 2019. Abstract 754.
ORLANDO – KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated unprecedented efficacy in the ZUMA-2 trial, according to an investigator involved in the study.
KTE-X19 produced a 93% overall response rate in patients with relapsed/refractory mantle cell lymphoma (MCL). This is the highest reported response rate in patients who have failed treatment with a Bruton’s tyrosine kinase (BTK) inhibitor, said Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr. Wang presented results from ZUMA-2 at the annual meeting of the American Society of Hematology.
“Patients with relapsed/refractory MCL have very poor outcomes,” Dr. Wang noted. “In patients who progress after BTK inhibition therapy, the overall response rate is only between 25% and 42%, and the overall survival is only between 6 and 10 months. Few patients proceed to allogeneic transplantation.”
The phase 2 ZUMA-2 trial was designed to test KTE-X19 in these patients. KTE-X19 is an anti-CD19 CAR T-cell therapy containing a CD3-zeta T-cell activation domain and a CD28 signaling domain. KTE-X19 is distinct from axicabtagene ciloleucel (KTE-C19) because the manufacturing process for KTE-X19 removes circulating tumor cells.
The trial enrolled 74 patients, and 68 of them received KTE-X19. Manufacturing failed for three patients, two patients died of progressive disease before they could receive KTE-X19, and one patient was found to be ineligible for treatment.
The 68 patients had a median age of 65 years (range, 38-79 years), and 84% were men. A majority of patients (85%) had stage IV disease and classical (59%) or blastoid (25%) morphology. Most patients (69%) had a Ki-67 proliferation index of 50% or greater, and most (56%) were intermediate- or high-risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI).
Patients had received a median of three prior therapies (range, one to five). All had been treated with a BTK inhibitor, with 85% receiving ibrutinib, 24% receiving acalabrutinib, and 9% receiving both. Most patients (68%) were refractory to BTK inhibition, and 32% relapsed on or after BTK inhibitor therapy.
In this study, patients could receive bridging therapy to keep their disease stable while KTE-X19 was being manufactured. There were 25 patients who received bridging therapy, which consisted of ibrutinib (n = 14), acalabrutinib (n = 5), dexamethasone (n = 12), and/or methylprednisolone (n = 2). Six patients received both BTK inhibitors and steroids.
All patients received conditioning with fludarabine and cyclophosphamide, followed by a single infusion of KTE-X19 at 2x106.
Efficacy
Sixty patients were evaluable for efficacy, and the median follow-up was 12.3 months (range, 7.0-32.3 months).
The overall response rate was 93%, with 67% of patients achieving a complete response and 27% achieving a partial response. Three percent of patients had stable disease, and 3% had progressive disease.
“The overall response rate was consistent across key subgroups, without any statistical difference,” Dr. Wang said. “This includes Ki-67, MIPI, and prior use of either steroids or bridging therapy.”
The median time to response was 1.0 month, and the median time to complete response was 3.0 months. Responses deepened over time, with 35% of patients converting from a partial response to a complete response, and 5% converting from stable disease to complete response.
The median duration of response has not been reached. At last follow-up, 57% of all patients and 78% of complete responders were still in response.
The median progression-free and overall survival have not been reached. At 12 months, the progression-free survival rate was 61%, and the overall survival rate was 83%.
Safety
All 68 patients were evaluable for safety. The most common adverse events were pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypotension (51%).
Grade 3/4 adverse events included pyrexia (13%), neutropenia (85%), thrombocytopenia (51%), anemia (50%), hypotension (22%), hypoxia (21%), hypophosphatemia (22%), fatigue (1%), and headache (1%).
There were two grade 5 treatment-related adverse events – organizing pneumonia on day 37 and staphylococcal bacteremia on day 134.
Cytokine release syndrome (CRS) occurred in 91% of patients, with 15% experiencing grade 3 or higher CRS. Patients were treated with tocilizumab or corticosteroids, and all CRS events resolved.
Neurologic adverse events occurred in 63% of patients, with grade 3 or higher events occurring in 31%. Neurologic events were treated with tocilizumab or corticosteroids, and 86% of neurologic events resolved.
This trial was sponsored by Kite, a Gilead company. Dr. Wang reported financial relationships with Kite and other companies.
SOURCE: Wang M et al. ASH 2019. Abstract 754.
ORLANDO – KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated unprecedented efficacy in the ZUMA-2 trial, according to an investigator involved in the study.
KTE-X19 produced a 93% overall response rate in patients with relapsed/refractory mantle cell lymphoma (MCL). This is the highest reported response rate in patients who have failed treatment with a Bruton’s tyrosine kinase (BTK) inhibitor, said Michael L. Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr. Wang presented results from ZUMA-2 at the annual meeting of the American Society of Hematology.
“Patients with relapsed/refractory MCL have very poor outcomes,” Dr. Wang noted. “In patients who progress after BTK inhibition therapy, the overall response rate is only between 25% and 42%, and the overall survival is only between 6 and 10 months. Few patients proceed to allogeneic transplantation.”
The phase 2 ZUMA-2 trial was designed to test KTE-X19 in these patients. KTE-X19 is an anti-CD19 CAR T-cell therapy containing a CD3-zeta T-cell activation domain and a CD28 signaling domain. KTE-X19 is distinct from axicabtagene ciloleucel (KTE-C19) because the manufacturing process for KTE-X19 removes circulating tumor cells.
The trial enrolled 74 patients, and 68 of them received KTE-X19. Manufacturing failed for three patients, two patients died of progressive disease before they could receive KTE-X19, and one patient was found to be ineligible for treatment.
The 68 patients had a median age of 65 years (range, 38-79 years), and 84% were men. A majority of patients (85%) had stage IV disease and classical (59%) or blastoid (25%) morphology. Most patients (69%) had a Ki-67 proliferation index of 50% or greater, and most (56%) were intermediate- or high-risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI).
Patients had received a median of three prior therapies (range, one to five). All had been treated with a BTK inhibitor, with 85% receiving ibrutinib, 24% receiving acalabrutinib, and 9% receiving both. Most patients (68%) were refractory to BTK inhibition, and 32% relapsed on or after BTK inhibitor therapy.
In this study, patients could receive bridging therapy to keep their disease stable while KTE-X19 was being manufactured. There were 25 patients who received bridging therapy, which consisted of ibrutinib (n = 14), acalabrutinib (n = 5), dexamethasone (n = 12), and/or methylprednisolone (n = 2). Six patients received both BTK inhibitors and steroids.
All patients received conditioning with fludarabine and cyclophosphamide, followed by a single infusion of KTE-X19 at 2x106.
Efficacy
Sixty patients were evaluable for efficacy, and the median follow-up was 12.3 months (range, 7.0-32.3 months).
The overall response rate was 93%, with 67% of patients achieving a complete response and 27% achieving a partial response. Three percent of patients had stable disease, and 3% had progressive disease.
“The overall response rate was consistent across key subgroups, without any statistical difference,” Dr. Wang said. “This includes Ki-67, MIPI, and prior use of either steroids or bridging therapy.”
The median time to response was 1.0 month, and the median time to complete response was 3.0 months. Responses deepened over time, with 35% of patients converting from a partial response to a complete response, and 5% converting from stable disease to complete response.
The median duration of response has not been reached. At last follow-up, 57% of all patients and 78% of complete responders were still in response.
The median progression-free and overall survival have not been reached. At 12 months, the progression-free survival rate was 61%, and the overall survival rate was 83%.
Safety
All 68 patients were evaluable for safety. The most common adverse events were pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypotension (51%).
Grade 3/4 adverse events included pyrexia (13%), neutropenia (85%), thrombocytopenia (51%), anemia (50%), hypotension (22%), hypoxia (21%), hypophosphatemia (22%), fatigue (1%), and headache (1%).
There were two grade 5 treatment-related adverse events – organizing pneumonia on day 37 and staphylococcal bacteremia on day 134.
Cytokine release syndrome (CRS) occurred in 91% of patients, with 15% experiencing grade 3 or higher CRS. Patients were treated with tocilizumab or corticosteroids, and all CRS events resolved.
Neurologic adverse events occurred in 63% of patients, with grade 3 or higher events occurring in 31%. Neurologic events were treated with tocilizumab or corticosteroids, and 86% of neurologic events resolved.
This trial was sponsored by Kite, a Gilead company. Dr. Wang reported financial relationships with Kite and other companies.
SOURCE: Wang M et al. ASH 2019. Abstract 754.
REPORTING FROM ASH 2019
An off-the-shelf drug to rival CAR T cells: ‘very exciting’
ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.
For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.
But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.
The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.
“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.
However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).
This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
Clinical trial results
Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.
“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.
All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.
Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.
Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.
The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.
“Some patients have remained in remission without additional therapy for more than a year,” he commented.
In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.
He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.
Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.
Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.
Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.
Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”
“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”
Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.
She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”
Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”
There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
How would it be used clinically?
In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.
Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.
Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.
This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.
Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.
So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.
“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.
Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.
Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
A version of this story originally appeared on Medscape.com.
ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.
For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.
But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.
The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.
“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.
However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).
This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
Clinical trial results
Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.
“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.
All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.
Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.
Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.
The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.
“Some patients have remained in remission without additional therapy for more than a year,” he commented.
In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.
He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.
Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.
Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.
Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.
Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”
“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”
Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.
She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”
Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”
There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
How would it be used clinically?
In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.
Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.
Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.
This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.
Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.
So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.
“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.
Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.
Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
A version of this story originally appeared on Medscape.com.
ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.
For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.
But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.
The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.
“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.
However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).
This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
Clinical trial results
Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.
“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.
All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.
Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.
Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.
The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.
“Some patients have remained in remission without additional therapy for more than a year,” he commented.
In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.
He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.
Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.
Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.
Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.
Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”
“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”
Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.
She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”
Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”
There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
How would it be used clinically?
In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.
Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.
Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.
This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.
Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.
So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.
“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.
Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.
Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
A version of this story originally appeared on Medscape.com.
Orelabrutinib could be ‘preferred’ BTK inhibitor for MCL
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
ORLANDO – A novel Bruton tyrosine kinase inhibitor has produced favorable results in patients with relapsed or refractory mantle cell lymphoma, according to findings presented at the annual meeting of the American Society of Hematology.
In a phase 2 trial, orelabrutinib produced an overall response rate of 86% and a 12-month progression-free survival rate of 64%. Safety results with orelabrutinib were superior to historical results with ibrutinib.
The efficacy and safety profile of orelabrutinib, as well as its “convenient” dosing, may make it the “preferred therapeutic choice for B-cell malignancy,” said Lijuan Deng, MD, PhD, of Peking University Cancer Hospital & Institute, Beijing, who presented the phase 2 trial of orelabrutinib at ASH 2019.
The trial enrolled 106 patients with relapsed/refractory mantle cell lymphoma who were treated at 22 centers in China. At baseline, the patients had a median age of 62 years (range, 37-73 years), and 79.2% were men. Most patients (94.4%) had stage III-IV disease.
Prior therapies included CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based (69.8%), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)-based (22.6%), DHAP (dexamethasone, cytarabine, and cisplatin)-based (22.6%), CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone)-based (12.3%), and ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin)-based (4.7%) regimens, and 88.7% of patients had received prior anti-CD20 therapy.
Patients received orelabrutinib at 100 mg twice daily (n = 20) or 150 mg once a day (n = 86). All 106 patients were evaluable for safety, and 99 were evaluable for efficacy.
Efficacy
“Orelabrutinib achieved high response and durable remissions,” Dr. Deng said.
The overall response rate was 85.9% in the evaluable efficacy population and 83.5% in the 150-mg dosing arm. The complete response rates were 27.3% and 29.1%, respectively. The median time to response, overall, was 1.9 months.
The median duration of response and median progression-free survival were not reached at a median follow-up of 10.5 months. At 12 months, 74.3% of patients were still in response, and the progression-free survival rate was 64%.
Safety
Most adverse events were grade 1-2 in nature. The most common grade 3 or higher events were platelet count decrease (11.3%), neutrophil count decrease (8.5%), anemia (7.5%), hypertension (3.8%), pneumonia (2.8%), white blood count decrease (1.9%), and hypokalemia (1.9%).
Adverse events of interest included grade 3 or higher hypertension (3.8%), diarrhea (6.6%), and infection (10.4%), as well as secondary malignancy (0.9%, n = 1). There were no cases of grade 3 or higher hemorrhage, grade 3 or higher atrial fibrillation/flutter, or grade 5 treatment-related adverse events.
Dr. Deng noted that rates of grade 3 or higher hemorrhage, atrial fibrillation, diarrhea, and infection, as well as rates of secondary malignancies, have historically been higher with ibrutinib (Blood. 2015 Aug 6;126[6]:739-45; Lancet. 2016 Feb 20;387[10020]:770-8).
“Orelabrutinib has an improved safety profile in patients with relapsed or refractory mantle cell lymphoma,” Dr. Deng said. “The most common adverse events were cytopenia and infections, which are considered mechanism based.”
The study was sponsored by InnoCare Pharma. Dr. Deng reported having no conflicts of interest.
SOURCE: Deng L et al. ASH 2019, Abstract 755.
REPORTING FROM ASH 2019
Study halted; ‘hyperprogression’ seen with nivolumab for R/R PTCL
ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.
An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.
“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.
The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.
They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.
Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.
The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.
All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.
As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.
The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.
“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.
Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.
The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.
“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.
“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.
“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.
The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.
SOURCE: Bennani NN et al. ASH 2019, Abstract 467.
ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.
An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.
“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.
The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.
They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.
Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.
The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.
All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.
As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.
The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.
“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.
Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.
The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.
“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.
“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.
“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.
The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.
SOURCE: Bennani NN et al. ASH 2019, Abstract 467.
ORLANDO – There is an urgent need for new therapies to treat relapsed or refractory peripheral T-cell lymphoma, but results of a phase 2 study suggest that monotherapy with the immune checkpoint inhibitor nivolumab (Opdivo) is not the hoped-for salvage treatment.
An interim analysis of data on 12 patients with peripheral T-cell lymphoma (PTCL) treated with nivolumab monotherapy showed an overall response rate of 33%, consisting of 2 complete responses and 2 partial responses. But the responses were short lived, and one patient had hyperprogressive disease – dramatic progression within one cycle of treatment – while two more had progression within two cycles, leading to a trial halt, reported N. Nora Bennani, MD, from the Mayo Clinic in Rochester, Minn.
“These findings likely reflect the distinct biology of PTCL and should be considered when designing future studies using checkpoint inhibitors in these diseases,” she said at the annual meeting of the American Society of Hematology.
The rationale for using an immune checkpoint inhibitor directed against the programmed death–1 protein and its ligands (PD and PD-L1/2) is that malignant cells in PTCL induce a profoundly immunosuppressive tumor microenvironment. Checkpoint inhibitors have shown strong activity against relapsed Hodgkin lymphoma, and the Mayo Clinic researchers speculated that an anti-PD-1 agent could have a similar effect in PTCL.
They had originally planned to enroll 29 patients into a phase 2 trial with nivolumab delivered 240 mg every 2 weeks for eight cycles, followed by a dose of 480 mg given every 4 weeks until disease progression or intolerable toxicities.
Patients were eligible if they had biopsy-confirmed relapsed or refractory PTCL, measurable disease on cross-sectional imaging of at least 1.5 cm, and prior systemic chemoimmunotherapy and/or autologous stem cell transplantation.
The interim analysis included 12 patients who received at least one dose of nivolumab. Of the 12 patients, 6 had angioimmunoblastic T-cell lymphoma (AITL), 3 had PTCL not otherwise specified, and 1 each had ALK-negative anaplastic large cell lymphoma (ALK-ALCL), enteropathy-associated T-cell lymphoma (EATL), or hepatosplenic gamma/delta T-cell lymphoma.
All patients had Ann Arbor stage III/IV disease, and 11 had extranodal involvement.
As noted, there were 4 responses among the 12 patients, consisting of 1 complete response in the patient with ALK-ALCL and 1 in a patient with AITL, and 2 partial responses – 1 in a patient with PTCL-NOS, and 1 in the patient with EATL.
The median progression-free survival for all 12 patients was short at 2.7 months, and the median overall survival was estimated at 6.7 months.
“It was staggering to see this: The duration of response was significantly short, less than 2 months,” Dr. Bennani said.
Nonhematologic toxicities were seen in 5 of the 12 patients (42%), and hematologic adverse events occurred in 3 (25%). All patients are now off treatment, 10 because of disease progression, 1 because of acute pancreatitis, and the aforementioned patient with hyperprogressive disease.
The patient with hyperprogressive disease had significant progression in tonsillar and cervical lymphadenopathy within 7-10 days of nivolumab infusion, with biopsy-proven AITL in the involved nodes.
“I believe that, in this patient population, combination therapies will be key. I think checkpoint blockers alone are not going to be sufficient to see meaningful outcomes in these patients,” Dr. Bennani said in an interview.
“An overall response rate of 33% is significant, because most other agents that were FDA approved in this patient population have response rates around 30%,” she said, adding that it’s possible that the patients with rapid progression had disease too advanced to be effectively treated with a checkpoint inhibitor.
“Ideally however, if we want to move forward, it will need to be with combinations of checkpoint inhibitors with HDAC [histone deacetylase] inhibitors, hypomethylating agents, or even PI3 kinase inhibitors,” she said.
The study was supported by Bristol-Myers Squibb. Dr. Bennani reported research funding and advisory board activities for Bristol-Myers Squibb and others.
SOURCE: Bennani NN et al. ASH 2019, Abstract 467.
REPORTING FROM ASH 2019
Care coordination, equity can eliminate disparities for nonwhite patients with DLBCL
ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.
Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.
He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.
“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.
Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.
The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.
The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.
The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.
They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.
Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.
Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.
Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.
The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.
In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.
In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.
For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.
Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”
The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.
SOURCE: Hu B et al. ASH 2019. Abstract 425.
ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.
Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.
He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.
“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.
Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.
The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.
The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.
The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.
They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.
Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.
Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.
Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.
The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.
In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.
In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.
For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.
Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”
The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.
SOURCE: Hu B et al. ASH 2019. Abstract 425.
ORLANDO – Patients with diffuse large B-cell lymphoma (DLBCL) who are members of an ethnic or racial minority do not have worse outcomes than whites when they receive appropriate treatment and institutional support, a study on disparities in cancer care shows.
Although previous studies have shown that minorities with DLBCL have worse outcomes than do whites, results of a study comparing outcomes from 155 patients of white heritage with those of 41 patients from black, Hispanic, or other minority backgrounds found no significant differences in either progression-free survival (PFS) or overall survival in 2 years over follow-up, reported Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute, Atrium Health, in Charlotte, N.C.
He attributes the results to his center’s robust nurse navigation program, equal access among all patients – regardless of ability to pay – to standard treatments, and to the availability of clinical trial participation and stem cell transplantation.
“I think a key message is that if you are able to offer the same treatment and clinical trials to people irrespective of their race or socioeconomic status and can provide support, you can get equal outcomes as long as the biology is the same in both groups,” he said at a briefing prior to presentation of data in an oral abstract session at the annual meeting of the American Society of Hematology.
Dr. Ghosh pointed to four separate studies that showed that minority populations with DLBCL have worse outcomes than did whites, and noted that both uninsured and Medicaid-insured patients have also been shown to have poorer results, suggesting a role of socioeconomic factors in determining who gets optimum care and who does not.
The investigators compared PFS and OS among white and nonwhite patients with DLBCL treated in their institution, which has a safety-net cancer center. They also looked at the frequencies of clinical trial participation and stem cell transplantation between the groups.
The study included all patients with de novo DLBCL who presented to their center during January 2016–January 2019. They used patient-reported descriptors of race/ethnicity to create one of two cohorts: either self-identified whites (155 patients) or nonwhites (41), a group that included black patients, Hispanic patients, Asian Americans, and Native Americans.
The authors collected data on demographics, disease characteristics (including revised International Prognostic Index and double-hit status), insurance data, treatment, trial enrollment, progression, and death.
They found that nonwhites were significantly younger at diagnosis (median 56 vs. 64 years; P = .007), with an even distribution between the sexes in each group.
Two-thirds of both white and nonwhite patients had government insurance (Medicare or Medicaid). Of the remaining patients, 33% of white had private insurance, compared with 27% of nonwhites. No whites were uninsured, but 3 of the 41 nonwhites (7%) had no insurance.
Of the 155 white patients, 121 (86%) received nurse navigation services, as did 33 of 41 (81%) of nonwhites. The services include lodging assistance for homeless patients, transportation services for patients without cars, and care coordination among primary care physicians, oncologists, and other specialists. The services are part of the center’s standard practice, with excess costs, if any, folded into the budget, Dr. Ghosh said.
Looking at disease characteristics and treatment, the investigators found that risk profiles were similar between the groups. A higher percentage of whites had double-hit lymphoma (11% vs. 7%), but this difference was not statistically significant.
The investigators also found that in their program race was not a barrier to optimum therapy, with 96% of whites and 98% of nonwhites receiving frontline therapy with an anthracycline and rituximab-based regimen, and 4% and 2%, respectively received a non–anthracycline based regimen.
In each group, 39% of patients had disease that either relapsed or was refractory to frontline therapy.
In all, 11% of whites and 12% of nonwhites enrolled in clinical trials, 11% and 19%, respectively, underwent stem cell transplantation.
For patients with relapsed/refractory disease, the 2-year PFS rates were 60% for whites, and 63% for nonwhites, and the 2-year OS rates were 74% and 81%, respectively.
Dr. Ghosh and colleagues concluded that “our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants, and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.”
The study was internally funded. Dr. Ghosh reported consulting fees, research funding, speakers bureau activity, and/or honoraria from multiple companies.
SOURCE: Hu B et al. ASH 2019. Abstract 425.
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
Bispecific CAR T-cells yield high response rate in relapsed/refractory myeloma
ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.
The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.
Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.
“,” Dr. Hu said in a press conference.
Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.
He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.
Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.
“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.
The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.
In the phase 1 study, 22 patients received BM38 CAR T-cell infusions following a fludarabine and cyclophosphamide preconditioning regimen. The median patient age was 59 years, and 50% were male. Nearly three-quarters (72%) had a cytogenetic abnormality, and the median number of prior therapies approached four (range, two to nine prior therapies).
Twenty of the patients (90.9%) had a response: 12 who achieved stringent complete remission, 2 with very good partial response, 5 with partial responses, and 1 with a minimal response.
Of 9 patients with extramedullary disease, 8 achieved partial or complete elimination of tumors, Dr. Hu said in his presentation.
Cytokine release syndrome occurred in 20 patients (90.91%), 5 of whom experienced severe cases (22.73%), according to the reported data. There was no observed neurotoxicity, according to the report, while almost all had hematologic toxicities. Three experienced hepatotoxicity and one had nephrotoxicity, according to Dr. Hu.
The phase 1 study was supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project Fund of Hubei Province of China, and Cellyan Therapeutics. The senior author of the study was affiliated with Cellyan Therapeutics. Dr. Hu and coauthors reported that they had no relevant conflicts of interest to declare.
SOURCE: Li C et al. ASH 2019. Abstract 930.
ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.
The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.
Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.
“,” Dr. Hu said in a press conference.
Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.
He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.
Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.
“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.
The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.
In the phase 1 study, 22 patients received BM38 CAR T-cell infusions following a fludarabine and cyclophosphamide preconditioning regimen. The median patient age was 59 years, and 50% were male. Nearly three-quarters (72%) had a cytogenetic abnormality, and the median number of prior therapies approached four (range, two to nine prior therapies).
Twenty of the patients (90.9%) had a response: 12 who achieved stringent complete remission, 2 with very good partial response, 5 with partial responses, and 1 with a minimal response.
Of 9 patients with extramedullary disease, 8 achieved partial or complete elimination of tumors, Dr. Hu said in his presentation.
Cytokine release syndrome occurred in 20 patients (90.91%), 5 of whom experienced severe cases (22.73%), according to the reported data. There was no observed neurotoxicity, according to the report, while almost all had hematologic toxicities. Three experienced hepatotoxicity and one had nephrotoxicity, according to Dr. Hu.
The phase 1 study was supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project Fund of Hubei Province of China, and Cellyan Therapeutics. The senior author of the study was affiliated with Cellyan Therapeutics. Dr. Hu and coauthors reported that they had no relevant conflicts of interest to declare.
SOURCE: Li C et al. ASH 2019. Abstract 930.
ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.
The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.
Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.
“,” Dr. Hu said in a press conference.
Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.
He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.
Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.
“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.
The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.
In the phase 1 study, 22 patients received BM38 CAR T-cell infusions following a fludarabine and cyclophosphamide preconditioning regimen. The median patient age was 59 years, and 50% were male. Nearly three-quarters (72%) had a cytogenetic abnormality, and the median number of prior therapies approached four (range, two to nine prior therapies).
Twenty of the patients (90.9%) had a response: 12 who achieved stringent complete remission, 2 with very good partial response, 5 with partial responses, and 1 with a minimal response.
Of 9 patients with extramedullary disease, 8 achieved partial or complete elimination of tumors, Dr. Hu said in his presentation.
Cytokine release syndrome occurred in 20 patients (90.91%), 5 of whom experienced severe cases (22.73%), according to the reported data. There was no observed neurotoxicity, according to the report, while almost all had hematologic toxicities. Three experienced hepatotoxicity and one had nephrotoxicity, according to Dr. Hu.
The phase 1 study was supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project Fund of Hubei Province of China, and Cellyan Therapeutics. The senior author of the study was affiliated with Cellyan Therapeutics. Dr. Hu and coauthors reported that they had no relevant conflicts of interest to declare.
SOURCE: Li C et al. ASH 2019. Abstract 930.
REPORTING FROM ASH 2019
High complete response rate seen with novel CAR-T for myeloma
ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.
Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.
“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.
JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.
BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.
At ASH 2019, Dr. Madduri presented results from the phase 1b portion of the CARTITUDE-1 trial. The investigators enrolled patients with multiple myeloma with measurable diseases as assessed by M-protein or serum free light chain levels who had experienced disease progression on at least 3 prior lines of therapy, or whose disease was refractory to at least two lines of therapy with a proteasome inhibitor, immunomodulatory drug (IMiD), and an anti-CD38 antibody.
Patients underwent apheresis for T-cell collection, with bridging therapy allowed until the expanded T cells could be delivered.
Following T-cell depletion with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 over 3 days, patients received a single weight-based infusion (compared with fixed-dose infusions used with other CAR T cell constructs).
The dose was targeted at 0.75x106 CAR-positive cells/kg, with a target range of 0.5–1.0x106, administered 5-7 days after the start of the conditioning regimen.
A total of 29 patients, median age 60, were evaluable for the safety and efficacy endpoints. One-fourth of the patients had a high-risk cytogenetic profile. The patients had received a median of 5 prior lines of therapy, with one patient receiving 18 prior lines. Of the 29 patients, 25 (86%) had previously undergone autologous transplantation.
As noted before, the ORR after a median follow-up of 6 months was 100%, with 69% completer responses, 17% very good partial responses, and 14% partial responses. The median time to complete response was 1 month (range 1 to 9 months). All but two patients remained free of disease progression at the median 6-month follow-up.
Nearly all patients (27) developed cytokine release syndrome (CRS), and one patient with prolonged grade 4 CRS died from related complications 99 days after infusion.
The median time to onset of CRS was 7 days with more than 90% of cases occurring between days 5 and 9.
Neurotoxicities, specifically immune effector cell–associated neurotoxicity syndrome (ICANS), were infrequent in CRS, and when they did occur were generally low grade, with only 1 grade 3 ICANS event.
Asked in an interview whether the impressive response rates seen with JNJ-4528 might persist over time, Dr. Madduri acknowledged that follow-up is still relatively short.
“This product is unique in that has a CD8 central memory phenotype preferentially, and we’re hoping that this would play a central role in the durability of response because they’re memory cells, but I think at this time we don’t know,” she said.
The CARTITUDE-1 trial is funded by Janssen Research & Development. Dr. Madduri disclosed serving as a consultant to Janssen and to Takeda, Foundation Medicine, AbbVie, and Celgene.
SOURCE: Madduri D et al. ASH 2019. Abstract 577.
ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.
Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.
“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.
JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.
BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.
At ASH 2019, Dr. Madduri presented results from the phase 1b portion of the CARTITUDE-1 trial. The investigators enrolled patients with multiple myeloma with measurable diseases as assessed by M-protein or serum free light chain levels who had experienced disease progression on at least 3 prior lines of therapy, or whose disease was refractory to at least two lines of therapy with a proteasome inhibitor, immunomodulatory drug (IMiD), and an anti-CD38 antibody.
Patients underwent apheresis for T-cell collection, with bridging therapy allowed until the expanded T cells could be delivered.
Following T-cell depletion with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 over 3 days, patients received a single weight-based infusion (compared with fixed-dose infusions used with other CAR T cell constructs).
The dose was targeted at 0.75x106 CAR-positive cells/kg, with a target range of 0.5–1.0x106, administered 5-7 days after the start of the conditioning regimen.
A total of 29 patients, median age 60, were evaluable for the safety and efficacy endpoints. One-fourth of the patients had a high-risk cytogenetic profile. The patients had received a median of 5 prior lines of therapy, with one patient receiving 18 prior lines. Of the 29 patients, 25 (86%) had previously undergone autologous transplantation.
As noted before, the ORR after a median follow-up of 6 months was 100%, with 69% completer responses, 17% very good partial responses, and 14% partial responses. The median time to complete response was 1 month (range 1 to 9 months). All but two patients remained free of disease progression at the median 6-month follow-up.
Nearly all patients (27) developed cytokine release syndrome (CRS), and one patient with prolonged grade 4 CRS died from related complications 99 days after infusion.
The median time to onset of CRS was 7 days with more than 90% of cases occurring between days 5 and 9.
Neurotoxicities, specifically immune effector cell–associated neurotoxicity syndrome (ICANS), were infrequent in CRS, and when they did occur were generally low grade, with only 1 grade 3 ICANS event.
Asked in an interview whether the impressive response rates seen with JNJ-4528 might persist over time, Dr. Madduri acknowledged that follow-up is still relatively short.
“This product is unique in that has a CD8 central memory phenotype preferentially, and we’re hoping that this would play a central role in the durability of response because they’re memory cells, but I think at this time we don’t know,” she said.
The CARTITUDE-1 trial is funded by Janssen Research & Development. Dr. Madduri disclosed serving as a consultant to Janssen and to Takeda, Foundation Medicine, AbbVie, and Celgene.
SOURCE: Madduri D et al. ASH 2019. Abstract 577.
ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.
Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.
“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.
JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.
BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.
At ASH 2019, Dr. Madduri presented results from the phase 1b portion of the CARTITUDE-1 trial. The investigators enrolled patients with multiple myeloma with measurable diseases as assessed by M-protein or serum free light chain levels who had experienced disease progression on at least 3 prior lines of therapy, or whose disease was refractory to at least two lines of therapy with a proteasome inhibitor, immunomodulatory drug (IMiD), and an anti-CD38 antibody.
Patients underwent apheresis for T-cell collection, with bridging therapy allowed until the expanded T cells could be delivered.
Following T-cell depletion with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 over 3 days, patients received a single weight-based infusion (compared with fixed-dose infusions used with other CAR T cell constructs).
The dose was targeted at 0.75x106 CAR-positive cells/kg, with a target range of 0.5–1.0x106, administered 5-7 days after the start of the conditioning regimen.
A total of 29 patients, median age 60, were evaluable for the safety and efficacy endpoints. One-fourth of the patients had a high-risk cytogenetic profile. The patients had received a median of 5 prior lines of therapy, with one patient receiving 18 prior lines. Of the 29 patients, 25 (86%) had previously undergone autologous transplantation.
As noted before, the ORR after a median follow-up of 6 months was 100%, with 69% completer responses, 17% very good partial responses, and 14% partial responses. The median time to complete response was 1 month (range 1 to 9 months). All but two patients remained free of disease progression at the median 6-month follow-up.
Nearly all patients (27) developed cytokine release syndrome (CRS), and one patient with prolonged grade 4 CRS died from related complications 99 days after infusion.
The median time to onset of CRS was 7 days with more than 90% of cases occurring between days 5 and 9.
Neurotoxicities, specifically immune effector cell–associated neurotoxicity syndrome (ICANS), were infrequent in CRS, and when they did occur were generally low grade, with only 1 grade 3 ICANS event.
Asked in an interview whether the impressive response rates seen with JNJ-4528 might persist over time, Dr. Madduri acknowledged that follow-up is still relatively short.
“This product is unique in that has a CD8 central memory phenotype preferentially, and we’re hoping that this would play a central role in the durability of response because they’re memory cells, but I think at this time we don’t know,” she said.
The CARTITUDE-1 trial is funded by Janssen Research & Development. Dr. Madduri disclosed serving as a consultant to Janssen and to Takeda, Foundation Medicine, AbbVie, and Celgene.
SOURCE: Madduri D et al. ASH 2019. Abstract 577.
REPORTING FROM ASH 2019
The clinical impact of new approvals in sickle cell, MCL
In this edition of “How I Will Treat My Next Patient,” I highlight two recent drug approvals by the Food and Drug Administration – crizanlizumab for sickle cell patients with painful crises and zanubrutinib for mantle cell lymphoma (MCL) patients in relapse.
Crizanlizumab
P-selectin is an adhesion molecule expressed on activated vascular endothelial cells and platelets. It is a key molecule in the initiation of leukocyte rolling on vessel walls and promotes firm attachment and extravasation to underlying tissues during inflammation. Up-regulation of P-selectin on endothelial cells and platelets contributes to the cell-cell interactions involved in the pathogenesis of sickle cell pain crises.
The SUSTAIN study was a multisite, placebo-controlled, randomized phase 2 trial of two different dosage levels of intravenous crizanlizumab (2.5 mg/kg or 5 mg/kg for 52 weeks), a humanized anti–P-selectin antibody, examining its effect on pain crises in patients with sickle cell disease. The primary endpoint was the annual rate of sickle cell pain crises, with a variety of clinically relevant secondary endpoints. The target population had 2-10 pain crises in the 12 months before enrollment. Patients on a stable dose of hydroxyurea for at least the most recent 3 months were allowed to enter, but if patients were not receiving hydroxyurea, it could not be initiated during the trial. Patients who were undergoing chronic red-cell transfusion therapy were excluded.
Among 198 enrolled patients, 35% did not complete the 52 weeks of treatment. Discontinuations were equally balanced among patients assigned to the high-dose, low-dose, and placebo cohorts. Adverse events associated with crizanlizumab included back pain, nausea, pyrexia, and arthralgia. Serious adverse events occurred in 55 patients, with 5 deaths, all of which were unrelated to treatment. Crizanlizumab did not augment hemolysis or bacterial infections.
In the efficacy analysis, patients receiving high-dose crizanlizumab had a median annual rate of 1.63 health care visits for sickle cell pain crises, compared with 2.98 visits for placebo patients (P = .01). In comparison with placebo, high-dose crizanlizumab also delayed the first pain crisis after starting treatment (4.1 months vs. 1.4 months), delayed the median time to a second pain crisis, and decreased the median number of pain crises annually.
More than twice as many high-dose crizanlizumab patients had no pain crisis episodes, compared with placebo patients. In general, differences were more striking in patients who were not taking hydroxyurea and who had non–hemoglobin SS disease. Differences in the primary endpoint between low-dose crizanlizumab and placebo were numerically, but not statistically, different.
How these results influence practice
It has been over 20 years since a new agent (hydroxyurea) was approved for sickle cell patients and, despite its use, sickle cell pain crises remain a frequent problem. Pain crises are associated with worse quality of life and increased risk of death. A promising advance is badly needed, especially in an era in which sensitivity to providers’ role in the opioid addiction crisis is highly scrutinized and may contribute to future undertreatment of pain episodes. This is especially true for patients from areas with high levels of opioid misuse.
The SUSTAIN trial was international, multi-institutional, placebo-controlled, and inclusive. These attributes enhance the likelihood that crizanlizumab will enhance patient care in routine practice. As an intravenous agent, monitoring adherence and toxicity are less challenging than with hydroxyurea. Despite these factors, however, there are some concerns. Crizanlizumab was not free of toxicity, quality of life via the Brief Pain Inventory used in the trial was not improved, and changes in the pain-severity and pain-interference domains were small. Treatment in SUSTAIN ensued for 52 weeks, so the emergence of late neutralizing antibodies and late toxicities with longer-term therapy will require careful postmarketing assessment.
These concerns notwithstanding, anyone who has cared for sickle cell patients would be excited about the potential benefits crizanlizumab could bring to patient care.
Zanubrutinib
The FDA has approved zanubrutinib for the treatment of MCL in adult patients who have received at least one prior therapy. The approval is based on the results of two studies in which overall response rate was the primary endpoint.
BGB-3111-206 (NCT03206970) was a phase 2, open-label, multicenter, single-arm trial of 86 patients with MCL who received at least one prior therapy. Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity. BGB-3111-AU-003 (NCT 02343120) was a phase 1/2, open-label, dose-escalation trial of B-cell malignancies, including 32 previously treated MCL patients treated with zanubrutinib at 160 mg twice daily or 320 mg once daily.
In the phase 2 trial, 18fluorodeoxyglucose (FDG)–PET scans were required and the ORR was 84% (95% confidence interval, 74%-91%), with a complete response rate of 59% (95% CI, 48%-70%) and a median response duration of 19.5 months (95% CI, 16.6% to not estimable). In the phase 1/2 dose-escalation trial, FDG-PET scans were not required and the ORR was 84% (95% CI, 67%-95%), with a complete response rate of 22% (95% CI, 9%-40%) and a median response duration of 18.5 months (95% CI, 12.6% to not estimable). In both trials, median follow-up on study was about 18 months.
The most common adverse reactions were cytopenias, upper respiratory tract infection, rash, bruising, diarrhea, and cough. The most common serious adverse reactions were pneumonia in 11% and hemorrhage in 5% of patients. Of 118 MCL patients, 8 stopped therapy because of an adverse event, most frequently pneumonia (3.4%).
How these results influence practice
Unfortunately, the therapy of recurrent MCL is noncurative, because of the rapid development of treatment resistance. There are multiple single-and multiagent chemotherapy regimens that may be tried, many incorporating immunotherapy options such as anti-CD20- or Bruton tyrosine kinase (BTK)–targeted agents. Given the limited efficacy of these agents, temporary nature of remissions, and paucity of data comparing these various treatment options, participation in clinical trials is encouraged whenever possible.
Outside of a clinical trial, zanubrutinib joins ibrutinib and acalabrutinib as approved single-agent BTK inhibitors for adult MCL patients in relapse. The impressive ORR and response duration reported for zanubrutinib are similar to the results achieved with the other agents, but the toxicity pattern may be slightly different.
As in the treatment of hormonally sensitive breast cancer, clinicians and patients benefit when they have multiple similar, equally efficacious oral agents with slightly different toxicity patterns so that quality of life can be improved and treatment duration maximized before treatment resistance develops and a more toxic and/or inconvenient therapy needs to be employed.
Whether zanubrutinib has benefits beyond those for MCL patients in relapse will depend on the results of confirmatory trials and patient-reported outcome data.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I Will Treat My Next Patient,” I highlight two recent drug approvals by the Food and Drug Administration – crizanlizumab for sickle cell patients with painful crises and zanubrutinib for mantle cell lymphoma (MCL) patients in relapse.
Crizanlizumab
P-selectin is an adhesion molecule expressed on activated vascular endothelial cells and platelets. It is a key molecule in the initiation of leukocyte rolling on vessel walls and promotes firm attachment and extravasation to underlying tissues during inflammation. Up-regulation of P-selectin on endothelial cells and platelets contributes to the cell-cell interactions involved in the pathogenesis of sickle cell pain crises.
The SUSTAIN study was a multisite, placebo-controlled, randomized phase 2 trial of two different dosage levels of intravenous crizanlizumab (2.5 mg/kg or 5 mg/kg for 52 weeks), a humanized anti–P-selectin antibody, examining its effect on pain crises in patients with sickle cell disease. The primary endpoint was the annual rate of sickle cell pain crises, with a variety of clinically relevant secondary endpoints. The target population had 2-10 pain crises in the 12 months before enrollment. Patients on a stable dose of hydroxyurea for at least the most recent 3 months were allowed to enter, but if patients were not receiving hydroxyurea, it could not be initiated during the trial. Patients who were undergoing chronic red-cell transfusion therapy were excluded.
Among 198 enrolled patients, 35% did not complete the 52 weeks of treatment. Discontinuations were equally balanced among patients assigned to the high-dose, low-dose, and placebo cohorts. Adverse events associated with crizanlizumab included back pain, nausea, pyrexia, and arthralgia. Serious adverse events occurred in 55 patients, with 5 deaths, all of which were unrelated to treatment. Crizanlizumab did not augment hemolysis or bacterial infections.
In the efficacy analysis, patients receiving high-dose crizanlizumab had a median annual rate of 1.63 health care visits for sickle cell pain crises, compared with 2.98 visits for placebo patients (P = .01). In comparison with placebo, high-dose crizanlizumab also delayed the first pain crisis after starting treatment (4.1 months vs. 1.4 months), delayed the median time to a second pain crisis, and decreased the median number of pain crises annually.
More than twice as many high-dose crizanlizumab patients had no pain crisis episodes, compared with placebo patients. In general, differences were more striking in patients who were not taking hydroxyurea and who had non–hemoglobin SS disease. Differences in the primary endpoint between low-dose crizanlizumab and placebo were numerically, but not statistically, different.
How these results influence practice
It has been over 20 years since a new agent (hydroxyurea) was approved for sickle cell patients and, despite its use, sickle cell pain crises remain a frequent problem. Pain crises are associated with worse quality of life and increased risk of death. A promising advance is badly needed, especially in an era in which sensitivity to providers’ role in the opioid addiction crisis is highly scrutinized and may contribute to future undertreatment of pain episodes. This is especially true for patients from areas with high levels of opioid misuse.
The SUSTAIN trial was international, multi-institutional, placebo-controlled, and inclusive. These attributes enhance the likelihood that crizanlizumab will enhance patient care in routine practice. As an intravenous agent, monitoring adherence and toxicity are less challenging than with hydroxyurea. Despite these factors, however, there are some concerns. Crizanlizumab was not free of toxicity, quality of life via the Brief Pain Inventory used in the trial was not improved, and changes in the pain-severity and pain-interference domains were small. Treatment in SUSTAIN ensued for 52 weeks, so the emergence of late neutralizing antibodies and late toxicities with longer-term therapy will require careful postmarketing assessment.
These concerns notwithstanding, anyone who has cared for sickle cell patients would be excited about the potential benefits crizanlizumab could bring to patient care.
Zanubrutinib
The FDA has approved zanubrutinib for the treatment of MCL in adult patients who have received at least one prior therapy. The approval is based on the results of two studies in which overall response rate was the primary endpoint.
BGB-3111-206 (NCT03206970) was a phase 2, open-label, multicenter, single-arm trial of 86 patients with MCL who received at least one prior therapy. Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity. BGB-3111-AU-003 (NCT 02343120) was a phase 1/2, open-label, dose-escalation trial of B-cell malignancies, including 32 previously treated MCL patients treated with zanubrutinib at 160 mg twice daily or 320 mg once daily.
In the phase 2 trial, 18fluorodeoxyglucose (FDG)–PET scans were required and the ORR was 84% (95% confidence interval, 74%-91%), with a complete response rate of 59% (95% CI, 48%-70%) and a median response duration of 19.5 months (95% CI, 16.6% to not estimable). In the phase 1/2 dose-escalation trial, FDG-PET scans were not required and the ORR was 84% (95% CI, 67%-95%), with a complete response rate of 22% (95% CI, 9%-40%) and a median response duration of 18.5 months (95% CI, 12.6% to not estimable). In both trials, median follow-up on study was about 18 months.
The most common adverse reactions were cytopenias, upper respiratory tract infection, rash, bruising, diarrhea, and cough. The most common serious adverse reactions were pneumonia in 11% and hemorrhage in 5% of patients. Of 118 MCL patients, 8 stopped therapy because of an adverse event, most frequently pneumonia (3.4%).
How these results influence practice
Unfortunately, the therapy of recurrent MCL is noncurative, because of the rapid development of treatment resistance. There are multiple single-and multiagent chemotherapy regimens that may be tried, many incorporating immunotherapy options such as anti-CD20- or Bruton tyrosine kinase (BTK)–targeted agents. Given the limited efficacy of these agents, temporary nature of remissions, and paucity of data comparing these various treatment options, participation in clinical trials is encouraged whenever possible.
Outside of a clinical trial, zanubrutinib joins ibrutinib and acalabrutinib as approved single-agent BTK inhibitors for adult MCL patients in relapse. The impressive ORR and response duration reported for zanubrutinib are similar to the results achieved with the other agents, but the toxicity pattern may be slightly different.
As in the treatment of hormonally sensitive breast cancer, clinicians and patients benefit when they have multiple similar, equally efficacious oral agents with slightly different toxicity patterns so that quality of life can be improved and treatment duration maximized before treatment resistance develops and a more toxic and/or inconvenient therapy needs to be employed.
Whether zanubrutinib has benefits beyond those for MCL patients in relapse will depend on the results of confirmatory trials and patient-reported outcome data.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I Will Treat My Next Patient,” I highlight two recent drug approvals by the Food and Drug Administration – crizanlizumab for sickle cell patients with painful crises and zanubrutinib for mantle cell lymphoma (MCL) patients in relapse.
Crizanlizumab
P-selectin is an adhesion molecule expressed on activated vascular endothelial cells and platelets. It is a key molecule in the initiation of leukocyte rolling on vessel walls and promotes firm attachment and extravasation to underlying tissues during inflammation. Up-regulation of P-selectin on endothelial cells and platelets contributes to the cell-cell interactions involved in the pathogenesis of sickle cell pain crises.
The SUSTAIN study was a multisite, placebo-controlled, randomized phase 2 trial of two different dosage levels of intravenous crizanlizumab (2.5 mg/kg or 5 mg/kg for 52 weeks), a humanized anti–P-selectin antibody, examining its effect on pain crises in patients with sickle cell disease. The primary endpoint was the annual rate of sickle cell pain crises, with a variety of clinically relevant secondary endpoints. The target population had 2-10 pain crises in the 12 months before enrollment. Patients on a stable dose of hydroxyurea for at least the most recent 3 months were allowed to enter, but if patients were not receiving hydroxyurea, it could not be initiated during the trial. Patients who were undergoing chronic red-cell transfusion therapy were excluded.
Among 198 enrolled patients, 35% did not complete the 52 weeks of treatment. Discontinuations were equally balanced among patients assigned to the high-dose, low-dose, and placebo cohorts. Adverse events associated with crizanlizumab included back pain, nausea, pyrexia, and arthralgia. Serious adverse events occurred in 55 patients, with 5 deaths, all of which were unrelated to treatment. Crizanlizumab did not augment hemolysis or bacterial infections.
In the efficacy analysis, patients receiving high-dose crizanlizumab had a median annual rate of 1.63 health care visits for sickle cell pain crises, compared with 2.98 visits for placebo patients (P = .01). In comparison with placebo, high-dose crizanlizumab also delayed the first pain crisis after starting treatment (4.1 months vs. 1.4 months), delayed the median time to a second pain crisis, and decreased the median number of pain crises annually.
More than twice as many high-dose crizanlizumab patients had no pain crisis episodes, compared with placebo patients. In general, differences were more striking in patients who were not taking hydroxyurea and who had non–hemoglobin SS disease. Differences in the primary endpoint between low-dose crizanlizumab and placebo were numerically, but not statistically, different.
How these results influence practice
It has been over 20 years since a new agent (hydroxyurea) was approved for sickle cell patients and, despite its use, sickle cell pain crises remain a frequent problem. Pain crises are associated with worse quality of life and increased risk of death. A promising advance is badly needed, especially in an era in which sensitivity to providers’ role in the opioid addiction crisis is highly scrutinized and may contribute to future undertreatment of pain episodes. This is especially true for patients from areas with high levels of opioid misuse.
The SUSTAIN trial was international, multi-institutional, placebo-controlled, and inclusive. These attributes enhance the likelihood that crizanlizumab will enhance patient care in routine practice. As an intravenous agent, monitoring adherence and toxicity are less challenging than with hydroxyurea. Despite these factors, however, there are some concerns. Crizanlizumab was not free of toxicity, quality of life via the Brief Pain Inventory used in the trial was not improved, and changes in the pain-severity and pain-interference domains were small. Treatment in SUSTAIN ensued for 52 weeks, so the emergence of late neutralizing antibodies and late toxicities with longer-term therapy will require careful postmarketing assessment.
These concerns notwithstanding, anyone who has cared for sickle cell patients would be excited about the potential benefits crizanlizumab could bring to patient care.
Zanubrutinib
The FDA has approved zanubrutinib for the treatment of MCL in adult patients who have received at least one prior therapy. The approval is based on the results of two studies in which overall response rate was the primary endpoint.
BGB-3111-206 (NCT03206970) was a phase 2, open-label, multicenter, single-arm trial of 86 patients with MCL who received at least one prior therapy. Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity. BGB-3111-AU-003 (NCT 02343120) was a phase 1/2, open-label, dose-escalation trial of B-cell malignancies, including 32 previously treated MCL patients treated with zanubrutinib at 160 mg twice daily or 320 mg once daily.
In the phase 2 trial, 18fluorodeoxyglucose (FDG)–PET scans were required and the ORR was 84% (95% confidence interval, 74%-91%), with a complete response rate of 59% (95% CI, 48%-70%) and a median response duration of 19.5 months (95% CI, 16.6% to not estimable). In the phase 1/2 dose-escalation trial, FDG-PET scans were not required and the ORR was 84% (95% CI, 67%-95%), with a complete response rate of 22% (95% CI, 9%-40%) and a median response duration of 18.5 months (95% CI, 12.6% to not estimable). In both trials, median follow-up on study was about 18 months.
The most common adverse reactions were cytopenias, upper respiratory tract infection, rash, bruising, diarrhea, and cough. The most common serious adverse reactions were pneumonia in 11% and hemorrhage in 5% of patients. Of 118 MCL patients, 8 stopped therapy because of an adverse event, most frequently pneumonia (3.4%).
How these results influence practice
Unfortunately, the therapy of recurrent MCL is noncurative, because of the rapid development of treatment resistance. There are multiple single-and multiagent chemotherapy regimens that may be tried, many incorporating immunotherapy options such as anti-CD20- or Bruton tyrosine kinase (BTK)–targeted agents. Given the limited efficacy of these agents, temporary nature of remissions, and paucity of data comparing these various treatment options, participation in clinical trials is encouraged whenever possible.
Outside of a clinical trial, zanubrutinib joins ibrutinib and acalabrutinib as approved single-agent BTK inhibitors for adult MCL patients in relapse. The impressive ORR and response duration reported for zanubrutinib are similar to the results achieved with the other agents, but the toxicity pattern may be slightly different.
As in the treatment of hormonally sensitive breast cancer, clinicians and patients benefit when they have multiple similar, equally efficacious oral agents with slightly different toxicity patterns so that quality of life can be improved and treatment duration maximized before treatment resistance develops and a more toxic and/or inconvenient therapy needs to be employed.
Whether zanubrutinib has benefits beyond those for MCL patients in relapse will depend on the results of confirmatory trials and patient-reported outcome data.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
SOX11 shows value as diagnostic marker in MCL
SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.
Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.
The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.
The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.
“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”
With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.
“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.
The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.
SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.
SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.
Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.
The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.
The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.
“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”
With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.
“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.
The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.
SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.
SOX11 may be an accurate diagnostic marker for mantle cell lymphoma (MCL), allowing clinicians to distinguish it from other lymphoproliferative disorders, according to findings from a meta-analysis of 14 case-control studies.
Woojoo Lee, PhD, of Inha University, Incheon, Republic of Korea, and coinvestigators, evaluated the diagnostic accuracy of SOX11 immunohistochemistry for the diagnosis of MCL. The results were published in PLoS One.
The researchers searched major databases for studies that evaluated the use of SOX11 immunohistochemistry in patients with MCL and other lymphoproliferative disorders. After applying the search parameters, the team identified 383 studies, 14 of which were included in the meta-analysis. Various data were extracted from eligible studies, including the type and clonality of anti-SOX11 antibody, number of SOX11-positive lymphomas (MCLs and other lymphoproliferative disorders), specificity, sensitivity, and others. After combining the data, the investigators calculated pooled sensitivity, specificity, and area under the curve. Among the included studies, hairy cell leukemia, Burkitt’s lymphoma, and lymphoblastic lymphoma were common among patient populations. In total, clone MRQ-58 mouse antibodies were used in five study populations.
The researchers found that the pooled specificity was 0.95 (95% CI, 0.9-0.97), and sensitivity was 0.9 (95% CI, 0.86-0.92). There was statistically significant substantial heterogeneity observed for specificity, but not for sensitivity, the investigators reported.
“The results demonstrated that SOX11 was a potential diagnostic marker for MCL,” they wrote. “Meta-regression revealed a significant inverse relationship between specificity and proportions of [Burkitt’s lymphoma, lymphoblastic lymphoma, and hairy cell leukemia].”
With respect to antibody type, the clone MRQ-58 mouse antibody showed consistently high specificity in the clinical setting, despite observed heterogeneity.
“Future studies using MRQ-58 are needed to improve our understanding of the diagnostic accuracy of SOX11 immunohistochemistry for MCL,” the investigators wrote.
The study was funded by the Next-Generation BioGreen 21 program (Republic of Korea). The authors reported having no conflicts of interest.
SOURCE: Lee W et al. PLoS One. 2019 Nov 12. doi: 10.1371/journal.pone.0225096.
FROM PLOS ONE
