In Patients With Relapsed/Refractory DLBCL, Tafasitamab/Lenalidomide Combo Shines

Kami J. Maddocks, MD

Kami J. Maddocks, MD, professor, Clinical Internal Medicine, Division of Hematology, The Ohio State University, Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, discussed the efficacy and safety of tafasitamab (Monjuvi) in combination with lenalidomide ([evlimid]) as treatment of a 74-year-old man with diffuse large B-cell lymphoma (DLBCL).

The treatment option was discussed with a group of oncologists during a Targeted Oncology Case Based Peer Perspective event.

Targeted Oncology™: What are the options for second-line therapy in transplant ineligible patients with DLBCL?

MADDOCKS: The updated NCCN [National Comprehensive Cancer Network] guidelines for DLBCL for second-line treatment of patients who are not considered transplant eligible [recommend] R-GemOx [rituximab, gemcitabine, and oxaliplatin] for people who choose to use chemotherapy as a second-line [treatment].¹ Bendamustine/rituximab alone or with polatuzumab vedotin [Polivy] is also an option; that approval is for patients with more than or equal to 2 prior therapies,² but is commonly used for non–transplant-eligible patients as a second-line therapy. GDP [gemcitabine, dexamethasone, and cisplatin] and other gemcitabine-based regimens plus rituximab [are included as other recommended therapies] as well as the tafasitamab and lenalidomide combination, which was just approved.³

In certain circumstances, [physicians can use] brentuximab vedotin [Adcetris] for CD30-positive disease, bendamustine/rituximab alone, or ibrutinib [Imbruvica] in non-GCB [germinal center B-cell–like] DLBCL. Another agent was approved this summer, also as third-line and subsequent therapy, which was oral selinexor [Xpovio].⁴

Which data led to the approval of this regimen?

Tafasitamab [plus] lenalidomide was approved at the end of July of this past summer. The FDA granted accelerated approval to this combination for relapsed DLBCL based on an 80-patient study of the combination called L-MIND [NCT02399085].³

Tafasitamab is an engineered CD19 antibody [that] showed single-agent activity in a phase 1/2 study in relapsed/refractory non-Hodgkin lymphoma, including a few CRs [complete responses] in DLBCL.5 We know that lenalidomide has some activity in relapsed DLBCL, and preclinical data showed...some synergy with the combination of these 2 agents, which led to the phase 2 L-MIND study.⁶

This study was a single-arm, open-label, multicenter study for patients with relapsed/refractory disease who had received 1 to 3 prior regimens, so not extremely heavily pretreated. The patients had to be considered not eligible for high-dose therapy and autologous stem cell transplant, either because of comorbidities or because they failed therapy with their second-line regimen. Primary refractory patients were excluded from the= study after an amendment, so there were a small number of these patients included [19%].

Patients were treated with the [tafasitamab/lenalidomide] combination. They received antibody infusion once a week for the first 3 cycles in combination with a dose of [standard] lenalidomide at 25 mg, followed by 1 week off. After 3 cycles, they were converted to every other week infusions of tafasitamab. They had the combination therapy for 12 months, or a year of treatment, and then those patients who responded to therapy were able to, if they were tolerating it, [choose] to do a tafasitamab maintenance, where they got an antibody infusion once every other week.

The primary end point of the study was overall response rate [ORR] with other secondary end points of safety and other response parameters.

The primary results of the study showed a best overall response rate by the Independent Review Committee of 60%, with a CR rate of 43%. Most of [the patients with a CR who were analyzed], almost 90%, had PET-confirmed complete responses. The median duration of response of the entire cohort of patients was 21.7 months, with a median duration of response not reached in those patients who achieved CR.

The median PFS [progression-free survival] was 12.1 months, and the median overall survival [OS] was not reached, with an estimated 12-month OS rate of 75% and an 18-month rate of 64%.

The ORR in the GCB disease was 50%, and in non-GCB it was 70%. It wasn’t powered to detect the difference, but there were similar responses. There was a trend toward a little better in the ABC [activated B-cell–like group], but the GCB still had a 50% ORR.

In which patients would you use this combination?

I have used tafasitamab/lenalidomide as a first-line [therapy] at relapse in patients who are not transplant-eligible candidates. In the 82-year-old patient that relapses after R-CHOP, I would off er this as a line of therapy for that patient. I’ve recently used it in patients who have progressed after R-CHOP or relapsed after R-CHOP and received another second-line therapy, like R-GemOX, and not had a response or had a short response. I’d use this in that setting.

I’ve not personally used it in a primary refractory patient. I think I would have to consider it in an elderly patient as opposed to if somebody is primary refractory to chemotherapy. Using a salvage [regimen] like R-GemOx, I would not necessarily use this over that because I don’t expect a great response just using chemotherapy again. That might be a setting where I would also consider using the bendamustine/rituximab plus polatuzumab regimen, because the polatuzumab is different.

What are the safety concerns with the tafasitamab-containing regimen?

The most common toxicities were hematologic, such as neutropenia, anemia, thrombocytopenia, and febrile neutropenia. The most common nonhematologic toxicities included rash in about 30% of patients, diarrhea [32%], fatigue [15%], cough [21%], and fever [20%].

There were serious AEs [adverse events] in 51% of patients, with 19% considered to be treatment related. There was a 12% discontinuation rate due to AEs, and 9% of patients experienced AEs of interest, which included tumor flare, basal cell carcinoma, and an allergic dermatitis. Then there were 13%, or 4 deaths, that occurred on study, including an [instance of] sudden death, respiratory failure, and cardiac event.

When you look at the toxicities, they did improve significantly after that first year of treatment. For patients who made it through the tafasitamab/lenalidomide combination, there were a lot fewer AEs reported if they continued on tafasitamab monotherapy. Just looking at the [common] AEs—cytopenias, rash, diarrhea, and fatigue—those are also pretty common from what we see of lenalidomide.

When you look at the starting dose, lenalidomide was [administered at] 25 mg....About 45% of patients did require a dose reduction on the study, but nearly 80% were able to maintain at 20 mg or higher. The majority of dose reductions occurred just from 25 mg to 20 mg of lenalidomide. Growth factor [support] was allowed and was used in about half of patients. When you look at these AEs, the majority of the toxicity was due to cytopenia. That’s probably what you’re going to see if you use R-GemOx or [another standard regimen].

_References:

_{1. NCCN. Clinical Practice Guidelines in Oncology. B-cell Lymphomas, version 4.2020. Accessed August 13, 2020. https://bit.ly/35H3YW0}

_{2. FDA approves polatuzumab vedotin-piiq for diff use large B-cell lymphoma. FDA. Updated June 10, 2019. Accessed October 29, 2020. https://bit.ly/2HL9kYg}

_{3. FDA grants accelerated approval to tafasitamab-cxix for diff use large B-cell lymphoma. FDA. Updated August 3, 2020. Accessed October 29, 2020. https://bit.ly/34Emq2z}

_{4. FDA approves selinexor for relapsed/refractory diff use large B-cell lymphoma. FDA. Updated June 22, 2020. Accessed October 29, 2020. https://bit.ly/2TAF2tQ}

_{5. Jurczak W, Zinzani PL, Gaidano G, et al. Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Ann Oncol. 2018;29(5):1266-1272. doi:10.1093/annonc/mdy056}

_{6. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diff use large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):978-988. doi:10.1016/S1470-2045(20)30225-4}