The final five-year follow-up data from the Phase 2 L-MIND study demonstrates that tafasitamab (Monjuvi®; MorphoSys and Incyte) plus lenalidomide (Revlimid®; Celgene, a Bristol-Myers Squibb Company) followed by tafasitamab monotherapy provided prolonged, durable responses in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).[1]

This conclusion is based on data were featured as a late-breaking oral presentation (Abstract # CT022) at the American Association for Cancer Research (AACR) 2023 Annual Meeting, being held April 14-19, 2023 at the Orange County Convention Center in Orlando, Florida.[1]

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in adults worldwide. [2] The disease characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about 40% of patients not responding to initial therapy or relapsing thereafter [3], leading to a high medical need for new, effective therapies2, especially for patients who are not eligible for an autologous stem cell transplant in this setting.

The L-MIND studt was a single arm, open-label Phase 2 trial (NCT02399085) investigating the combination of tafasitamab, a humanized Fc-modified CD19 targeting immunotherapy,  and lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma who had at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., Rituximab (Rituxan®; Genentech/Biogen)), who were not eligible for high-dose chemotherapy or refused subsequent autologous stem cell transplant.

The study’s primary endpoint was overall response rate. Secondary outcome measures included duration of response, progression-free survival and overall survival. In May 2019, the study reached its primary completion.

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Meaningful
“Five-year data demonstrating durability of response is meaningful for oncologists as they consider the most appropriate treatment option for a patient,” said Johannes Duell, MD., University Hospital Würzburg Medical Clinic and Polyclinic.

“The prolonged and durable responses seen at five years among relapsed or refractory DLBCL patients in the L-MIND study show that the tafasitamab treatment regimen may have curative potential, which I look forward to seeing explored in future studies.”

Study results
At the data cut-off* for the full analysis set, which included 80 patients, the overall response rate (ORR) was 57.5% (95% CI = 45.9, 68.5), and a complete response (CR) was observed in 41.2% of patients (95% CI = 30.4, 51.6; n = 33). The study results also demonstrated a partial response (PR) in 16.2% of patients (95% CI = 8.9, 26.2; n =13).  The study results showed that the median duration of response (DOR) was not reached after a median follow up of 44.0 months (95% CI = 29.9, 57.0).

The median overall survival(OS) was 33.5 months (95% CI = 18.3, NR) and median progression-free survival (mPFS) was 11.6 months (95% CI = 5.7, 45.7). Of the 21 patients with >60 months of follow-up, 14 patients had received one prior line of therapy (pLoT), and seven patients had received ≥2 pLoT.

Patients with one pLoT (n = 40) had a higher ORR of 67.5% (CR = 52.5% and PR = 15%) compared to 47.5% of patients with two or more pLoT (n = 40; CR = 30% and PR = 17.5%)

Adverse events
The study analyses further showed that no new safety signals were identified. The majority of adverse events (AEs) were grade 1 or grade 2 during both combination and monotherapy treatment. Patients experienced a lower frequency of all-grade and grade 3 or higher adverse events during monotherapy.

The most common adverse events with combination therapy were neutropenia (incidence per person per year, all-grade/grade ≥3: 3.79/2.09) and thrombocytopenia (1.52/0.52), which declined after patients switched to monotherapy (all-grade/grade ≥3: 1.09/0.70 and 0.17/0.06, respectively, in the first two years of monotherapy). Neutropenia and diarrhea were the most common adverse events in the first two years of monotherapy.

“The totality of the long-term L-MIND data presented at AACR further reinforce our confidence that the tafasitamab plus lenalidomide combination remains the in-practice, outpatient, targeted immunotherapy option that can provide sustained remissions for patients with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant,” said Tim Demuth, M.D., Ph.D., Chief Research and Development Officer, MorphoSys.

“The durable responses and consistent safety profile observed in the five-year analysis are encouraging and further support the use of the Monjuvi regimen as a potentially curative option for appropriate patients.”

“The new five-year L-MIND data build on prior analyses that detail the potential for tafasitamab plus lenalidomide to provide long-term, meaningful responses for certain patients with relapsed or refractory DLBCL, a historically difficult-to-treat form of the disease,” noted Steven Stein, M.D., Chief Medical Officer, Incyte.

Regulatory
In July 2020, the U.S. Food and Drug Administration (FDA) approved tafasitamab in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for ASCT. This indication is approved under accelerated approval based on ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

The U.S. approval is based on an efficacy subgroup of 71 patients confirmed by central lab. The FDA decision represented the first approval of a second-line treatment for adult patients with DLBCL who progressed during or after first-line therapy. Tafasitamab, in combination with lenalidomide, was granted accelerated approval based on the one-year primary analysis of the L-MIND study. The data for the five-year analysis of the L-MIND study have not yet been submitted to, or reviewed by, the FDA.

Note: *The data cut-off for the full analyses set was November 14, 2022.

Clinical trial
A Study to Evaluate the Safety and Efficacy of Lenalidomide With MOR00208 in Patients With R-R DLBCL (L-MIND) – NCT02399085

Highlights of Prescribing information
Tafasitamab-cxix (Monjuvi®; MorphoSys and Incyte)[Prescribing Information]
Lenalidomide (Revlimid®; Celgene, a Bristol-Myers Squibb Company)[Prescribing Information]
Rituximab (Rituxan®; Genentech/Biogen and MabThera®; Roche)[Prescribing Information]

References
[1] Duell J, Abrisqueta P, Andre M, Augustin M, Gaidano G, González Barca E,  Jurczak W, Kalakonda N, Liberati AM, Maddocks KJ, Menne T, Nagy Z, Tournilhac O, Bakuli A, Amin A, Gurbanov K, Salles G. . Five-year efficacy and safety of tafasitamab in patients with relapsed or refractory DLBCL: Final results from the phase II L-MIND study. In: Proceedings of the 114th Annual Meeting of the American Association for Cancer Research; 2023 April 14-19; Orlando, FL. Philadelphia (PA): AACR; 2023. Abstract nr CT022
[2] Sarkozy C, Sehn LH. Management of relapsed/refractory DLBCL. Best Pract Res Clin Haematol. 2018 Sep;31(3):209-216. doi: 10.1016/j.beha.2018.07.014. Epub 2018 Jul 23. PMID: 30213390.
[3] Skrabek P, Assouline S, Christofides A, MacDonald D, Prica A, Sangha R, Matthews BA, Sehn LH. Emerging therapies for the treatment of relapsed or refractory diffuse large B cell lymphoma. Curr Oncol. 2019 Aug;26(4):253-265. doi: 10.3747/co.26.5421. Epub 2019 Aug 1. PMID: 31548805; PMCID: PMC6726277.

Featured image: AACR 2016 Annual Meeting. Photo courtesy 2016 – 2023 © AACR/Todd Buchanan.

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