Second-Line Polatuzumab Vedotin Plus R-ICE in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Produces High ORR

Pharmacy Times® interviewed Matthew J. Matasar, MD, MS, chief of blood disorders, Rutgers Cancer Institute of New Jersey and RWJBarnabas Health, on his poster presentation titled “Polatuzumab Vedotin Combined with R-ICE (PolaR-ICE) As Second-Line Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma” at the 64th American Society of Hematology (ASH) Annual Meeting and Exhibition in New Orleans, Louisiana.

Pharmacy Times®: Could you explain the individual functions of polatuzumab vedotin and R-ICE chemotherapy in the context of relapsed/refractory diffuse large B-cell lymphoma?

Matthew J. Matasar: So, despite ongoing progress in the treatment of relapsed large cell lymphoma with the advent of CAR T and other treatments, platinum-based chemotherapy remains the standard of care for patients with late relapsing diffuse large B cell lymphoma. R-ICE is a standard chemo immunotherapy program combining rituximab with the platinum chemotherapy platform of ICE, ifosfamide, carboplatin, and etoposide.

We know, however, that response rates to R-ICE are still suboptimal and outcomes could be improved, so we are testing the addition of polatuzumab vedotin to that combination. polatuzumab vedotin or Pola for short, is an antibody drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B-cells with a payload of MMAE which is an anti-tubulin agent.

Pharmacy Times®: What is the current standard of care for second-line therapy in relapsed/refractory diffuse, and where would combined with R-ICE (PolaR-ICE) fit in?

Matthew J. Matasar: So polatuzumab is FDA approved in the treatment of patients with relapsed large cell lymphoma who are not eligible for auto transplant in combination with bendamustine and rituximab. But for patients who are eligible for curative auto transplant, the standard of care has always been platinum chemotherapy, such as R-ICE.

Our hypothesis here is that the addition of polatuzumab to the R-ICE backbone can improve overall response rate and complete response rate and may represent a more potent option for getting patients who are eligible for transplant able to receive that transplant.

Pharmacy Times®: What was the eligibility criteria for the patient population enrolled in the phase 2 trial investigating the safety and efficacy of PolaR-ICE, and what were the study methods?

Matthew J. Matasar: So eligibility for our protocol was patients with relapsed aggressive B cell lymphoma, including de novo diffuse large B-cell lymphomas, as well as transformed indolent lymphomas and primary mediastinal lymphoma.

Pharmacy Times®: What did the phase 2 trial show regarding the safety and efficacy of PolaR-ICE in this patient population?

Matthew J. Matasar: So we've been very encouraged by our preliminary outcomes here with an overall response rate of approximately 90% and a complete response rate of approximately 60% to the platform as a second line treatment program. These are encouraging compared to what one would have expected from historical controls.

Obviously, this is a single arm phase 2 study, so it needs to be validated with a broader experience. But I'm very encouraged by the efficacy and activity of the program, particularly in the context of the toxicity.

Encouragingly, we did not see a lot of additional toxicity from the inclusion of polatuzumab on top of R-ICE. One of the more notable toxicities that is recognized in polatuzumab vedotin is neuropathy, but we saw a low rate of neuropathy at only 25%, and all but one of these cases were in grade 1 in severity, establishing it as a potentially safe program for further evaluation.

We know that the neurotoxicity of polatuzumab is really a cumulative one, and in this program, we are limiting the total exposure of polatuzumab. Patients will only receive 6 doses in total—2 or 3 doses pre transplant and for those that go on to receive an auto transplant, they complete a total of 6 doses of 3 or 4 doses in a post-transplant consolidated format, limiting the dose to only 6 cycles that we know is associated with manageable risks of neuropathy. And we know that the R-ICE platform itself is associated with lower rates of neuropathy as opposed to other platinum-based programs, such as those containing cisplatin, which was really the reason why we chose R-ICE as the backbone platinum program in this study.

Pharmacy Times®: What are next steps following these results?

Matthew J. Matasar: So obviously, we need to get further follow up of this cohort to see not just how many of them are able to respond and get to their transplant, but what do post-transplant outcomes look like. If, at the end of the day, we continue to be encouraged by this approach, it certainly does open the option to test this in a more formal fashion comparing it in a randomized program compared to standard of care platinum without polatuzumab vedotin, with key endpoints such as overall survival.