New Solutions Continue to Show Up in the Lymphoma Treatment Landscape

Matthew Matasar, MD

The field of treatment for patients with lymphoma diseases like follicular lymphoma or diffuse large B-cell lymphomas [DLBCL] has undergone some significant changes with the advent of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies, but challenges and questions remain.

In an interview with Targeted Oncology^TM, Matthew Matasar, MD, chief of the division of blood disorders at the Rutgers Cancer Institute and professor at the Rutgers Robert Wood Johnson Medical School, discussed the major highlights of treatment for this patient population in newer treatments like mosunetuzumab [Lunsumio], which was approved by the FDA for patients with relapsed/refractory follicular lymphoma.¹ Moreover, he breaks down recent data for patients with non-Hodgkin lymphoma and what new studies mean for this patient population now, and into the future.²

What is a top highlight for the field of follicular lymphoma?

For follicular lymphoma, we have important updates on the activity and durability of responses with the treatment with mosunetuzumab. Mosunetuzumab is a novel bispecific antibody targeting CD20 and CD3, creating an immune synapse with healthy T cells. This has been described in prior [meetings] and publications and clearly is an active medicine in patients with multimodal follicular lymphoma, with overall response rates [ORR] of 80% and complete response [CR] rates of 60%.

The important question, however, is how durable are these responses? We now have maturing data, with a median follow up now of 27 months, we see that the median duration of response, CR, and even median progression-free survival [PFS] have not yet been reached, which for me, emphasizes the point that not only is this agent highly active in relapsed FL, but the responses are quite durable.We need further follow up and certainly we have a lot more to learn, but we're looking forward to it's likely FDA approval and our ability to prescribe it in the clinic.

What about for patients with non-Hodgkin’s lymphoma?

In the area of non-Hodgkin lymphoma aggressive B-cell lymphoma, I presented work that we conducted with colleagues at the Dana Farber and City of Hope. Looking at improving treatments [in the] second line [for patients with] large cell lymphoma that are eligible for stem cell transplant. We know that even in this era of CAR T-cell therapy there are a subset of patients who should receive and benefit from platinum based chemoimmunotherapy with planned auto transplant in consolidation. [This is for those] with later relapsing large cell lymphoma those who ever relapse greater than 12 months beyond completion of first line therapy. That being said, the standard of care treatment has a sub optimal ORR to CR rate and we clearly need to do better for such patients.

What new data is there for this patient population?

We presented our phase 2 study called Pola-R-ICE, which incorporates the use of polatuzumab vedotion [and RICE (rituximab [Rituxan], ifosfamide, carboplatin and etoposide)], the antibody drug conjugate targeting CD79B, in combination with RICE for patients with relapsed large cell lymphoma who were eligible for subsequent consolidated stem cell transplant.2 Briefly, in the study patients received 2 or 3 cycles of the Pola-R-ICE treatment and those who had chemo-sensitive disease went on to receive a standard of care auto transplant, and then after transplant would receive polutuzumab monotherapy to complete a total of 6 doses. So, 3 doses if they got 3 cycles beforehand and 4 if they only required 2.

We showed high activity for this combination in this patient population despite a high-risk patient population putting many patients that currently would be shunted towards the CAR-T program, because of primary refractory or early relapsing disease. We nonetheless showed high ORR and CR rates and the ability to get patients to transplant. The data are still maturing, and we're looking to see what the impact of the consolidative treatment is going to look like in terms of durability of response, but very encouraging results that we were able to present.

What are your hopes for the future of treatment for patients with lymphoma?

In follicular lymphoma, clearly, we are coming upon the era of bispecific antibodies, with mosunetuzumab and competitive molecules that are being developed in this space as well. We're likely to find ourselves in a situation where we have multiple options in the treatment of [patients with] follicular lymphoma with bispecific antibodies. Important questions will remain, however, including both the durability of these agents as well as the optimal sequencing and which patients should be getting CAR T-cell therapy, which patients be getting bispecific antibodies, and how do these agents work in sequence? And how can we optimize the course of care for a patient navigating through follicular lymphoma?

In DLBCL, there's clearly still a lot of work to be done in clarifying the optimal second line treatment program for patients who should be receiving the stem cell transplant, as well as further innovation that's required in terms of novel ways of assessing response. [Other questions remain such as] should we be incorporating [minimal residual disease] decision making into the transplant decision making apparatus? And how can we best incorporate other novel therapies into multi agent programs, again, with the intention of improving outcomes for our patients with highest risk disease.

_REFERENCES

_{1. FDA approves Genentech’s Lunsumio, a first-in-class bispecific antibody, to treat people with relapsed or refractory follicular lymphoma. News release. December 23, 2022. Accessed March 1, 2023. https://bit.ly/3WJw6B3}

_{2. Herrera A, Chen L, Crombie J, et al. Polatuzumab vedotin combined with r-ice (polar-ice) as second-line therapy in relapsed/refractory diffuse large b-cell lymphoma}._{. Blood (2022) 140 (Supplement 1): 1065–1067. doi.org/10.1182/blood-2022-165699}