Praveen Ramakrishnan, MD, assistant professor, Department of Internal Medicine, UT Southwestern Harold C. Simmons Comprehensive Cancer Center, discusses the negative results from the phase 3 BELINDA trial (NCT03570892) and its effect on the use of CAR T-cell products in aggressive B-cell non-Hodgkin lymphoma (NHL).

The BELINDA trial evaluated the efficacy and safety of tisagenlecleucel (tisa-cel; Kymriah) vs the current standard of care, which was salvage chemotherapy combined with autologous hematopoietic stem cell transplantation. Results showed that tisa-cel did not significantly improve outcomes in patients with relapsed/refractory NHL compared with standard treatment.

There are several potential explanations for these negative results, Ramakrishnan continues. The trial was subject to a delay in CAR T-cell product manufacturing, causing some patients scheduled to receive tisa-cel to experience prolonged wait time. In the interim, these patients were subjected to more chemotherapy, potentially skewing results. Moreover, it is possible that the highest-risk patients were selected out by investigators due to this concern.

Cross-trial comparisons are notoriously difficult to conduct, Ramakrishnan notes. It is unclear if the results from BELINDA indicate that tisa-cel is inferior to other CAR T-cell therapies such as lisocabtagene maraleucel (liso-cel; Breyanzi) and axicabtagene ciloleucel (axi-cel; Yescarta). However, both these therapies are approved for this patient population in the second-line setting, while tisa-cel is only approved for patients in the third-line setting and beyond.

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Praveen Ramakrishnan, MD, discusses the negative results from the phase 3 BELINDA trial and its effect on the use of CAR T-cell products in aggressive B-cell non-Hodgkin lymphoma.
 

Dr. Ramakrishnan on Negative Results of the BELINDA Trial in Non-Hodgkin Lymphoma

Praveen Ramakrishnan, MD,an assistant professorin the Department of Internal Medicineat UT Southwestern Medical Center, discusses the promising direction of biosimilars in hematology.

At UT Southwestern Medical Center, investigators are trying to maximize the use of biosimilars based on FDA approvals, says Ramakrishnan. In terms of growth factor support, biosimilars have already been adopted in the treatment of patients with hematologic malignancies, Ramakrishnan adds. Althoughthe use of biosimilars has not yet been implemented in the transplant setting, many believe that they are here to stay because they offer cost savings with equivalent outcomes, says Ramakrishnan.

Additionally, there is aPharmacy and Therapeutics Committee for the oncology service and hematologic malignancies service. Regular meetings are held so that biosimilar products are carefully analyzed and discussed prior to any approval for use at the UT Southwestern Medical Center. During these meetings, the data with these products are examined closely, discussed and debated, concludes Ramakrishnan.

Praveen Ramakrishnan, MD, discusses the promise of biosimilars in hematology. 

Dr. Ramakrishnan on the Promise of Biosimilars in Hematology

Praveen Ramakrishnan, MD, assistant professor, Department of Internal Medicine, UT Southwestern Medical Center, discusses updates in diffuse large B-cell lymphoma (DLBCL) that were presented at the 2019 ASH Annual Meeting.

The Intergroup National Clinical Trials Network S1001 study evaluated whether 4 cycles of chemotherapy could abate the need for further treatment or radiation in patients with limited-stage DLBCL. The results showed excellent outcomes with limited-duration chemotherapy, says Ramakrishnan. Taken collectively with the results of the FLYER trial, the field is beginning to question the role of radiation, especially in patients with good-risk, limited-stage DLBCL. As such, chemotherapy and limited-duration chemotherapy will likely become the standard, says Ramakrishnan.

Additionally, Stephen J. Schuster, MD, of the Perelman School of Medicine, University of Pennsylvania, presented an abstract on mosunetuzumab, which is an anti-CD20 bispecific T-cell engager (BiTE) that was evaluated in heavily refractory large cell lymphoma. The study included patients who were refractory following CAR T-cell therapy. Even so, investigators reported impressive responses in this difficult-to-treat population. As such, BiTEs could offer another avenue of treatment after CAR T-cell therapy, concludes Ramakrishnan.

Dr. Ramakrishnan on Updates in DLBCL

Praveen Ramakrishnan, MD, assistant professor, Department of Internal Medicine, UT Southwestern Medical Center, discusses CAR T-cell therapy in patients with mantle cell lymphoma (MCL).

CAR T-cell therapy is a novel agent being explored in heavily pretreated patients with relapsed/refractory lymphomas. Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, presented on the ZUMA-2 trial (NCT02601313) at the 2019 ASH Annual Meeting. This study utilized the anti-CD19 KTE-X19 product. The CAR T-cell product looks very promising, says Ramakrishnan.

The ZUMA-2 trial enrolled patients with MCL who had received ≤5 prior lines of therapy, which must have included an anti-CD20 antibody, chemotherapy, and a BTK inhibitor. Sixty-seven percent of patients experienced a complete remission rate. It is an exciting time to be practicing as a lymphoma doctor, concludes Ramakrishnan.

Praveen Ramakrishnan, MD, discusses CAR T-cell therapy in patients with mantle cell lymphoma (MCL).

Dr. Ramakrishnan on Use of CAR T-Cell Therapy in MCL

Praveen Ramakrishnan, MD, assistant professor, Department of Internal Medicine, UT Southwestern Medical Center, discusses the benefit of CAR T-cell therapy in patients with mantle cell lymphoma (MCL).

At the 2019 ASH Annual Meeting, Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, presented the results of the phase II ZUMA-2 trial. In the trial, investigators evaluated KTE-X19, an anti-CD19 CAR T-cell therapy, in patients with relapsed/refractory MCL who received 1 to 5 prior therapies. The 12-month PFS and OS rates were 61% (95% CI, 45%-74%) and 83% (95% CI, 71%-91%), respectively.

The results are very promising and demonstrate the viability of CAR T-cell therapy in a difficult-to-treat patient population, concludes Ramakrishnan.

Praveen Ramakrishnan, MD, discusses the benefit of CAR T-cell therapy in patients with mantle cell lymphoma.

Praveen Ramakrishnan, MD

Articles

Dr. Ramakrishnan on Negative Results of the BELINDA Trial in Non-Hodgkin Lymphoma

Dr. Ramakrishnan on the Promise of Biosimilars in Hematology

Dr. Ramakrishnan on Updates in DLBCL

Dr. Ramakrishnan on Use of CAR T-Cell Therapy in MCL

Dr. Ramakrishnan on Benefit of CAR T-Cell Therapy in MCL