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The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.
“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.
His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.
“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.
This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.
Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.
Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.
Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.
Dr. Park said that the biggest difference between the two therapies is that CAR T requires but a single infusion of a living drug. Patients do need to stay close to treatment centers to receive treatment for toxicities, but after about 28 days, they can go home and be monitored from a distance. Furthermore, patients may start by receiving 1 million T-cells, but those cells exponentially expand 100,000- to 1,000,000-fold, meaning that the T-cells to treat cancer have the potential to persist for months and sometimes years.
Furthermore, results from ZUMA-3 Trial of the CD19-targeting CAR T-Cell therapy brexucabtagene autoleucel (Tecartus; Kite Pharma) suggest that CAR T outperforms Mini-HCVD + Ino +/-Blina in patients with r/r ALL. Participants in the trial showed an overall response rate around 80%, a 71% complete response rate, and a median OS of 25.4 months. Patients who achieved a complete response had an even better median OS of 47 months. Although this was not a head-to-head trial with Mini-HCVD + Ino +/-Blina, if the plateau of long-term survivors continues, “this drug could be set apart from treatment with monoclonal antibodies,” Dr. Park said.
However, brexucabtagene autoleucel is not a cure or even an option for all patients. Some patients are too frail to get the drug, and they risk experiencing cytokine release syndrome (CRS). Data from the FELIX study suggest that the CAR T-cell treatment Obe-cel could offer a safety profile that reduces the risk of serious side effects while remaining effective at treating r/r ALL. Obe-cel showed efficacy very similar to that of brexucabtagene autoleucel, with a 70%-80% response rate, and only 2% of patients experienced CRS.
Dr. Park noted that the next frontier in CAR T-cell therapy is figuring out which patients will respond well to CAR T and which are going to need more treatment after CAR T. However, he noted that evidence suggests patients with low MRD are likely to do best on CAR T and that bispecific antibodies can help patients get to what might be the best chance at a cure for r/r ALL, namely CAR-T.
The moderator of the debate, Jessica Altman, MD, professor of medicine, hematology oncology division, Feinberg School of Medicine at Northwestern University in Chicago, noted: “My take home is that antibody therapy and CAR-T will be sequenced and used together.” She noted that blinatumomab is moving into the front line of therapy, as in the E1910 trials, and how this treatment allows for study and use of CAR T earlier in the care of patients “when there may be less toxicity and higher response.”
Jabbour concluded on a similar note, adding that the “cure for this disease will happen in our lifetime. We will shorten therapy by doing immunotherapy upfront followed by CAR T consolidation and no more transplantation. I don’t think antibodies immunotherapies or CAR T need be competitive, they can be used in a complimentary fashion.”
Jabbour reported no financial disclosures. Park disclosed ties with Allogene, Artiva Biotherapeutics, Amgen, Affyimmune, BeBiopharma, Beigene, Bright Pharmaceuticals, Autolus, Caribou Biosciences, Galapagos, Kite, Medpace, Minerva Biotechnologies, Pfizer, Servier, Sobi, and Takeda. Neither Altman nor Shastri reported any disclosures.
The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.
“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.
His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.
“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.
This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.
Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.
Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.
Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.
Dr. Park said that the biggest difference between the two therapies is that CAR T requires but a single infusion of a living drug. Patients do need to stay close to treatment centers to receive treatment for toxicities, but after about 28 days, they can go home and be monitored from a distance. Furthermore, patients may start by receiving 1 million T-cells, but those cells exponentially expand 100,000- to 1,000,000-fold, meaning that the T-cells to treat cancer have the potential to persist for months and sometimes years.
Furthermore, results from ZUMA-3 Trial of the CD19-targeting CAR T-Cell therapy brexucabtagene autoleucel (Tecartus; Kite Pharma) suggest that CAR T outperforms Mini-HCVD + Ino +/-Blina in patients with r/r ALL. Participants in the trial showed an overall response rate around 80%, a 71% complete response rate, and a median OS of 25.4 months. Patients who achieved a complete response had an even better median OS of 47 months. Although this was not a head-to-head trial with Mini-HCVD + Ino +/-Blina, if the plateau of long-term survivors continues, “this drug could be set apart from treatment with monoclonal antibodies,” Dr. Park said.
However, brexucabtagene autoleucel is not a cure or even an option for all patients. Some patients are too frail to get the drug, and they risk experiencing cytokine release syndrome (CRS). Data from the FELIX study suggest that the CAR T-cell treatment Obe-cel could offer a safety profile that reduces the risk of serious side effects while remaining effective at treating r/r ALL. Obe-cel showed efficacy very similar to that of brexucabtagene autoleucel, with a 70%-80% response rate, and only 2% of patients experienced CRS.
Dr. Park noted that the next frontier in CAR T-cell therapy is figuring out which patients will respond well to CAR T and which are going to need more treatment after CAR T. However, he noted that evidence suggests patients with low MRD are likely to do best on CAR T and that bispecific antibodies can help patients get to what might be the best chance at a cure for r/r ALL, namely CAR-T.
The moderator of the debate, Jessica Altman, MD, professor of medicine, hematology oncology division, Feinberg School of Medicine at Northwestern University in Chicago, noted: “My take home is that antibody therapy and CAR-T will be sequenced and used together.” She noted that blinatumomab is moving into the front line of therapy, as in the E1910 trials, and how this treatment allows for study and use of CAR T earlier in the care of patients “when there may be less toxicity and higher response.”
Jabbour concluded on a similar note, adding that the “cure for this disease will happen in our lifetime. We will shorten therapy by doing immunotherapy upfront followed by CAR T consolidation and no more transplantation. I don’t think antibodies immunotherapies or CAR T need be competitive, they can be used in a complimentary fashion.”
Jabbour reported no financial disclosures. Park disclosed ties with Allogene, Artiva Biotherapeutics, Amgen, Affyimmune, BeBiopharma, Beigene, Bright Pharmaceuticals, Autolus, Caribou Biosciences, Galapagos, Kite, Medpace, Minerva Biotechnologies, Pfizer, Servier, Sobi, and Takeda. Neither Altman nor Shastri reported any disclosures.
The comparative benefits and limitations of these two treatments for r/r ALL were a topic for discussion at the Great Debates & Updates Hematological Malignancies conference, held April 5-6 in New York City.
“Every single patient with ALL should benefit from bispecific antibodies before getting CAR-T cells, and I want to make the case that everybody should get CAR T as well. But they should get blinatumomab before they get CAR T,” said Elias Jabbour, MD, of the MD Anderson Cancer Center at The University of Texas in Houston, whose presentation focused on the merits of bispecific antibodies.
His argument was based on data indicating that patients have better chances of long-term remission with the use of bispecific antibodies when they are administered in an earlier round of salvage treatment — and the fact that patients who are not cured with these drugs can still achieve a lower disease burden and perform better on CAR T-cell therapy than those who don’t receive the drugs.
“When blinatumomab is used as a consolidation during the first salvage treatment and spaces out transplantation, 3-year overall survival increases in the relapse setting, deepening responses and reducing the rate of VOD (veno-occlusive disease). The safety and efficacy of CAR T depends on a disease burden. If you have a minimal residual disease (MRD), you have a safer outcome and a better outcome in the long run,” Dr. Jabbour explained.
This point of view is supported by data from the treatment of patients r/r ALL with low intensity chemotherapy + inotuzumab ozogamicin (Besponsa; Pfizer) +/- blinatumomab (Blincyto; Amgen), knows as Mini-HCVD + Ino +/-Blina. Trial members achieved a median overall survival (OS) rate of 17 months, a 3-year survival rate of 42%, and an overall MRD negativity rate of 85%.
Dr. Jabbour noted that blinatumomab has its limitations. Generally, this treatment is administered intravenously every few weeks and can be cumbersome for patients who must travel to an infusion center. However, data from a phase 1b trial of single agent subcutaneous blinatumomab for advanced ALL has demonstrated that this formulation can be effective and can lead to MRD negativity, possibly paving the way for easier administration of the drug.
Aditi Shastri, MD, a leukemia specialist at New York’s Montefiore Medical Center who attended the debate, agreed that the data presented did support Dr. Jabbour’s contention that subcutaneous blinatumomab could make treatment available to even more people with r/r ALL. “It’s easier to administer than the blina pump and could act as a bridge to curative therapies like AlloHSCT,” she said.
Jae Park, MD, a leukemia and cellular therapy specialist at Memorial Sloan Kettering Cancer Center in New York City, argued that CAR T is the most potent therapy for r/r ALL. Dr. Park agreed that inotuzumab and blinatumomab have yielded tremendous progress in the treatment of patients with r/r ALL, but he noted that bispecific antibodies lack some of the advantages of CAR T.
Dr. Park said that the biggest difference between the two therapies is that CAR T requires but a single infusion of a living drug. Patients do need to stay close to treatment centers to receive treatment for toxicities, but after about 28 days, they can go home and be monitored from a distance. Furthermore, patients may start by receiving 1 million T-cells, but those cells exponentially expand 100,000- to 1,000,000-fold, meaning that the T-cells to treat cancer have the potential to persist for months and sometimes years.
Furthermore, results from ZUMA-3 Trial of the CD19-targeting CAR T-Cell therapy brexucabtagene autoleucel (Tecartus; Kite Pharma) suggest that CAR T outperforms Mini-HCVD + Ino +/-Blina in patients with r/r ALL. Participants in the trial showed an overall response rate around 80%, a 71% complete response rate, and a median OS of 25.4 months. Patients who achieved a complete response had an even better median OS of 47 months. Although this was not a head-to-head trial with Mini-HCVD + Ino +/-Blina, if the plateau of long-term survivors continues, “this drug could be set apart from treatment with monoclonal antibodies,” Dr. Park said.
However, brexucabtagene autoleucel is not a cure or even an option for all patients. Some patients are too frail to get the drug, and they risk experiencing cytokine release syndrome (CRS). Data from the FELIX study suggest that the CAR T-cell treatment Obe-cel could offer a safety profile that reduces the risk of serious side effects while remaining effective at treating r/r ALL. Obe-cel showed efficacy very similar to that of brexucabtagene autoleucel, with a 70%-80% response rate, and only 2% of patients experienced CRS.
Dr. Park noted that the next frontier in CAR T-cell therapy is figuring out which patients will respond well to CAR T and which are going to need more treatment after CAR T. However, he noted that evidence suggests patients with low MRD are likely to do best on CAR T and that bispecific antibodies can help patients get to what might be the best chance at a cure for r/r ALL, namely CAR-T.
The moderator of the debate, Jessica Altman, MD, professor of medicine, hematology oncology division, Feinberg School of Medicine at Northwestern University in Chicago, noted: “My take home is that antibody therapy and CAR-T will be sequenced and used together.” She noted that blinatumomab is moving into the front line of therapy, as in the E1910 trials, and how this treatment allows for study and use of CAR T earlier in the care of patients “when there may be less toxicity and higher response.”
Jabbour concluded on a similar note, adding that the “cure for this disease will happen in our lifetime. We will shorten therapy by doing immunotherapy upfront followed by CAR T consolidation and no more transplantation. I don’t think antibodies immunotherapies or CAR T need be competitive, they can be used in a complimentary fashion.”
Jabbour reported no financial disclosures. Park disclosed ties with Allogene, Artiva Biotherapeutics, Amgen, Affyimmune, BeBiopharma, Beigene, Bright Pharmaceuticals, Autolus, Caribou Biosciences, Galapagos, Kite, Medpace, Minerva Biotechnologies, Pfizer, Servier, Sobi, and Takeda. Neither Altman nor Shastri reported any disclosures.
FROM GREAT DEBATES & UPDATES HEMATOLOGIC MALIGNANCIES