Tafasitamab/Lenalidomide Combo Induces Impressive Response Rates in Relapsed/Refractory DLBCL

Among limited therapeutic options, the recent approval of the combination of tafasitamab-cxix (Monjuvi) and lenalidomide (Revlimid) is a significant advance in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), said Kami J. Maddocks, MD.

On July 31, 2020, the FDA approved the doublet for the treatment of patients with relapsed/refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, and for patients who are not eligible for autologous stem cell transplant (ASCT).¹

The approval was based on findings from the phase 2 L-MIND trial in which the combination induced a 55% overall response rate (ORR), including a 37% complete response (CR) rate and an 18% partial response rate.² Additionally, the median duration of response was 21.7 months.

“The approval of this combination has the potential to play a large role in relapsed/refractory DLBCL,” said Maddocks, lead study author of the pivotal trial. “It is the first therapy approved in the second-line setting and it was studied in a population of patients who are not candidates for ASCT. For those patients who are older or have medical comorbidities and are not candidates for intensive salvage therapy and ASCT, this combination offers an effective, safe, and potentially durable option.”

In an interview with OncLive, Maddocks, an associate professor of clinical internal medicine in the Division of Hematology at the Ohio State University Comprehensive Cancer Center–James, discussed the clinical implications of the approval of tafasitamab and lenalidomide in relapsed/refractory DLBCL, as well as remaining challenges that future research efforts should address.

OncLive: What is the current treatment landscape of relapsed/refractory DLBCL?

Maddocks: The current treatment approach for patients with relapsed/refractory DLBCL depends somewhat on the patient’s age and their ability to tolerate treatment. Patients who are candidates for potentially curative therapy receive salvage chemotherapy and ASCT. Patients who are not candidates typically will enroll in a clinical trial or receive palliative chemotherapy.

Polatuzumab vedotin-piiq (Polivy) [in combination with] bendamustine and rituximab (Rituxan; BR) was approved [in June 2019] in patients who fail 1 salvage therapy. CAR T-cell therapy is also used in this setting. Typically, CAR T-cell therapy is reserved for patients who had the intent of going to ASCT but were unable to due to lack of response to salvage therapy. [CAR T-cell therapy] is also being evaluated in high-risk patients in first-line relapse.

What was the rationale for combining tafasitamab and lenalidomide in this patient population?

We know lenalidomide is an oral immunomodulator that has activity in different hematologic malignancies, including DLBCL. Some retrospective data have suggested that [lenalidomide] benefits [patients with] non-germinal center (GC) type DLBCL compared with GC-type DLBCL.

Tafasitamab is an anti–CD19-directed agent that showed single-agent activity in a phase 2 study. A few patients with DLBCL [in that study] had a complete response (CR). CD19 is expressed across all B cells, so it makes a good target for B-cell malignancies.

Some preclinical rationale suggested that [because of] the way these [agents] work on the immune system, there can be some synergistic activity. The 2 agents were tried as a combination given their potential synergy and single-agent activity.

Could you discuss the data from the L-MIND trial that led to the approval of the combination?

The L-MIND study was a single-arm, phase 2 trial that used the combination of tafasitamab and lenalidomide. Initially, the trial reported a 60% ORR with 40% of patients achieving a CR. This was fairly high activity in a relapsed/refractory DLBCL population. The median progression-free survival of the entire population was 16.2 months. However, for those patients who achieved a CR, the duration of response was almost 3 years, which is a fairly durable response in this patient population.

In general, the toxicities [of the combination] were fairly manageable. They were similar to what we’ve seen with lenalidomide alone. Infusion-related reactions were [confined to] grade 1/2.

Is any additional research planned with this combination?

There is actually a study that is evaluating the combination of tafasitamab and lenalidomide in the frontline setting. There is a phase 3 study evaluating standard R-CHOP versus R-CHOP plus tafasitamab and lenalidomide to see if this is a potential benefit to patients in the outpatient setting.

What challenges remain in relapsed/refractory DLBCL treatment, and where should future research efforts be focused?

There are still a lot of unmet needs in both the [up-front] and relapsed/refractory settings in DLBCL. We know that we cure about 60% to 70% of patients with DLBCL with standard R-CHOP. However, this leaves 30% to 40% of patients who relapse from their disease. Certainly, improving frontline therapy to provide curative therapy in the up-front setting to more patients is an unmet need.

For those patients who are relapsed/refractory to [R-CHOP], tafasitamab/lenalidomide has offered them an option. However, there is still potential for improved or curative therapies in this setting. One of the other big unmet needs is for those patients who relapse after CAR T-cell therapy. For patients who either go to ASCT then CAR T-cell therapy or those patients who go to CAR T as a potentially curative option but either do not respond or relapse after, have very limited treatment options. This is an area that we need to focus our efforts on to look for effective therapies in these patients.

References:

1. FDA approves Monjuvi (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). [News release]. MorphoSys AG. July 31, 2020. Accessed August 13, 2020. https://bwnews.pr/3jZhE5g.
2. Maddocks KJ, Duell J, Gonzalez Barca E, et al. Update of the single-arm phase II L-MIND study of MOR208 + lenalidomide (LEN) in relapsed/refractory diffuse large B-cell lymphoma (R-R DLBCL): response rates in patient subgroups with poor prognosis. J Clin Oncol. 2019;37(suppl 15):7521. doi:10.1200/JCO.2019.37.15_suppl.7521