Tafasitamab Plus Lenalidomide Has Continued Efficacy and Safety in R/R DLBCL

The combination of tafasitamab-cxix (Monjuvi) and lenalidomide (Revlimid) followed by tafasitamab maintenance prolonged responses in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to results from the final, 5-year follow-up analysis of the phase 2 L-MIND trial (NCT02399085), which were presented at the 2023 AACR Annual Meeting.¹

In all treated patients, the overall response rate (ORR) was 57.5% (95% CI, 45.9%-68.5%), including a complete response (CR) rate of 41.3% and a partial response (PR) rate of 16.3% (n = 13; 95% CI, 8.9%-26.2%). Additionally, 16.3% of patients each achieved a best response of stable disease (SD) and progressive disease (PD), and responses were other/missing in 10.1% of patients.

“The 5-year analysis of the phase 2 L-MIND study shows durable responses in patients with relapsed/refractory DLBCL who are not eligible for autologous stem cell transplant [ASCT],” Nagesh Kalakonda, MBBS, MRCP, FRCPath, PhD, of the University of Liverpool, United Kingdom, said in a presentation of the data.

Previous findings from L-MIND, which led to the 2020 FDA approval of tafasitamab plus lenalidomide in the second-line setting in patients with relapsed/refractory DLBCL, demonstrated an ORR of 55% with the combination, including a CR rate of 37% and a PR rate of 18%.² Additionally, 3-year follow-up data from this trial showed an ORR rate of 57.5% (95% CI, 45.9%-68.5%) with tafasitamab plus lenalidomide, which was comprised of a CR in 40% of patients and a PR in 17.5% of patients.³

In this single-arm trial, eligible patients included those at least 18 years of age with relapsed/refractory DLBCL that was ineligible for ASCT.1 Patients could have received 1 to 3 prior systemic therapies, and needed to have an ECOG performance status of 0 to 2. Patients with primary refractory DLBCL were not eligible, although 15 patients with refractory disease were included in earlier phases of the study.

During cycles 1 through 3, patients received tafasitamab at 12 mg/kg once weekly for 28-day cycles. During cycles 4 through 12, patients received tafasitamab at 12 mg/kg every 2 weeks. During cycles 1 through 12, patients also received 25 mg of oral lenalidomide daily on days 1 through 21 of each cycle. Patients who achieved at least SD by cycle 12 continued to receive 12 mg/kg of tafasitamab maintenance every 2 weeks and were treated until disease progression.

L-MIND had a primary end point of centrally-assessed ORR. The key secondary end points were progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety.

In total, 81 patients were enrolled, and 80 patients received the study treatment. Of these patients, 1 discontinued tafasitamab because of an adverse effect (AE). Discontinuations of both tafasitamab and lenalidomide occurred in 8, 2, 32, 2, 1, and 1 patients because of AEs, death, disease relapse/PD, patient withdrawal, investigator/clinician decision, and general deterioration, respectively. In total, 30 patients completed 12 cycles of tafasitamab plus lenalidomide, and 4 patients discontinued lenalidomide because of AEs.

Beyond cycle 12, 34 patients continued tafasitamab monotherapy. Of those patients, 6, 10, 6, and 4 discontinued treatment because of AEs, disease relapse/PD, patient withdrawal, and investigator/clinician decision, respectively. Eight patients received tafasitamab until the end of the study per protocol.

In the overall population, the median age was 72.0 years (range, 41.0-86.0), with 56.2% of patients (n = 45) over 70 years of age at baseline. Additionally, 53.8% of patients (n = 43) were male. In total, 75% of patients (n = 60) had Ann Arbor stage III to IV disease, 50% of patients (n = 40) had an International Prognostic Index score of 3 to 5, 55.0% of patients (n = 44) had elevated lactate dehydrogenase, and 11.2 % of patients (n = 9) had received prior ASCT.

In the patients with 1 prior line of therapy (n = 40), the ORR was 67.5% (95% CI, 45.9%-79.4%), including respective CR, PR, SD, PD, and missing/other rates of 52.5%, 15%, 17.5%, 12.5%, and 2.5%. In the patients with at least 2 prior lines of therapy (n = 40), the ORR was 47.5% (95% CI, 31.5%-63.9%), including respective CR, PR, SD, PD, and missing/other rates of 30%, 17.5%, 15%, 20%, and 17.5%.

Overall, the median DOR was not reached (NR; 95% CI, 33.8%-NR) with a median follow-up of 44.0 months (95% CI, 29.9-57.0). In patients with 1 prior line of therapy, the median DOR was NR (95% CI, 9.1-NR) with a median follow-up of 53.8 months (95% CI, 24.4-58.7). In patients with at least 2 prior lines of therapy, the median DOR was NR (95% CI, 26.1-NR) with a median follow-up of 38.9 months (95% CI, 12.8-59.4).

The median PFS in the overall population was 11.6 months (range, 5.7-45.7) with a median follow-up of 45.6 months (95% CI, 22.9-57.6). In patients with 1 prior line of therapy, the median PFS was 23.5 months (95% CI, 7.4-NR) with a median follow-up of 57.6 months (95% CI, 26.5-60.7). In patients with at least 2 prior lines of therapy, the median PFS was 7.6 months (95% CI, 2.7-45.5) with a median follow-up of 33.9 months (95% CI, 10.9-46.8).

In the overall population, the median OS was 33.5 months (95% CI, 18.3-NR) with a median follow-up of 45.6 months (95% CI, 22.9-57.6). In patients with 1 prior line of therapy, the median OS was NR (95% CI, 24.6-NR) with a median follow-up of 57.6 months (95% CI, 26.5-60.7). In patients with at least 2 prior lines of therapy, the median OS was 15.5 months (95% CI, 8.6-45.5) with a median follow-up of 33.9 months (95% CI, 10.9-46.8).

Of the 26 patients who ended treatment with a response, 23 ended with a CR and 3 ended with a PR. Two patients, both with a CR, died from PD. Three patients, 1 with a CR and 2 with a PR, died from reasons other than DLBCL. In total, 4 patients, all of whom achieved a CR, received a subsequent anti-lymphoma therapy, 2 of whom died from PD thereafter.

In the patients who received lenalidomide with or without tafasitamab, 345 hematological and 851 non-hematological treatment-emergent AEs (TEAEs) occurred. Of the 52 patients who received tafasitamab monotherapy for up to 2 years, 76 and 383 hematological and non-hematological TEAEs occurred, respectively. Of the 27 patients who received tafasitamab monotherapy for more than 2 years, 46 and 347 hematological and non-hematological TEAEs occurred, respectively.

The hematological TEAEs that occurred in the patients who received the combination therapy or lenalidomide alone were neutropenia (n = 167 events), thrombocytopenia (n = 67), anemia (n = 54), leukopenia (n = 35), febrile neutropenia (n = 10), lymphopenia (n = 7), agranulocytosis (n = 2), lymphadenopathy (n = 2), and hypoglobulinemia (n = 1). The hematological TEAEs that occurred in the patients who received tafasitamab monotherapy for up to 2 years were neutropenia (n = 39), thrombocytopenia (n = 6), anemia (n = 15), leukopenia (n = 9), febrile neutropenia (n = 3), lymphopenia (n = 2), hypoglobulinemia (n = 1), and thrombocytosis (n = 1). The hematological TEAEs that occurred in the patients who received tafasitamab monotherapy for more than years were neutropenia (n = 18), thrombocytopenia (n = 5), anemia (n = 13), leukopenia (n = 3), lymphopenia (n = 2), agranulocytosis (n = 1), hypoglobulinemia (n = 1), thrombocytosis (n = 1), leukocytosis (n = 1), and iron deficiency anemia (n = 1).

The most common non-hematological TEAEs in the patients who received the combination therapy or lenalidomide alone were diarrhea (n = 40 events), peripheral edema (n = 28), asthenia (n = 24), hypokalemia (n = 23), pyrexia (n = 21), nausea (n = 19), fatigue (n = 18), cough (n = 17), increased blood creatinine (n = 17), constipation (n = 16), dyspnea (n = 16), hypocalcemia (n = 16), decreased appetite (n = 14), muscle spasms (n = 14), hypomagnesemia (n = 12), bronchitis (n = 12), back pain (n = 10), vomiting (n = 10), urinary tract infection (n = 10), and increased c-reactive protein (n = 10). The most common non-hematological TEAEs in the patients who received tafasitamab monotherapy for up to 2 years were diarrhea (n = 20), asthenia (n = 10), pyrexia (n = 12), nausea (n = 19), fatigue (n = 11), cough (n = 11), and decreased appetite (n = 10). The most common non-hematological TEAEs in the patients who received tafasitamab monotherapy for more than 2 years were diarrhea (n = 13), pyrexia (n = 10), cough (n = 10), hypomagnesemia (n = 11), and hyperglycemia (n = 10).

In the patients who received the combination therapy or lenalidomide alone, important TEAEs of interest included neutropenia/leukopenia (n = 243 events), thrombocytopenia (n = 70), anemia (n = 54), infections and infestations of grade 3 or higher (n = 26), infusion-related reactions (n = 4), secondary primary malignancies (n = 3), hepatitis B reactivation (n = 1), progressive multifocal leukoencephalopathy (n = 1), and cytokine release syndrome (n = 1). In the patients who received tafasitamab monotherapy for up to 2 years, important TEAEs of interest included neutropenia/leukopenia (n = 57), thrombocytopenia (n = 8), anemia (n = 15), infections and infestations of grade 3 or higher (n = 12), infusion-related reactions (n = 1), secondary primary malignancies (n = 5), and hepatitis B reactivation (n = 1). In the patients who received tafasitamab monotherapy for more than years, important TEAEs of interest included neutropenia/leukopenia (n = 24), thrombocytopenia (n = 5), anemia (n = 13), infections and infestations of grade 3 or higher (n = 10), secondary primary malignancies (n = 9), and hepatitis B reactivation (n = 1).

“We suggest that this treatment may have durable responses in this group of patients, and some of them may have been cured,” Kalakonda concluded.

Disclosures: Dr Kalakonda reports Speaker’s Bureau roles with BMS/Celgene, Gilead/Kite, Hospira, Incyte, Janssen, Karyopharm, Roche, and Takeda; and grant/research support from Celgene, Gilead, and Roche.

References

1. Duell J, Abrisqueta P, Andre M, et al. Five-year efficacy and safety of tafasitamab in patients with relapsed or refractory DLBCL: final results from the phase II L-MIND study. Presented at: 2023 AACR Annual Meeting; April 14-19, 2023l Orlando, FL. Abstract CT022.
2. 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). July 31, 2020. Accessed April 16, 2023. https://www.businesswire.com/news
3. Duell J, Maddocks KJ, Gonzalez-Barca E, et al. Long-term analyses from L-MIND, a phase II study of tafasitamab (MOR208) combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). J Clin Oncol. Published online May 28, 2021. doi:10.1200/JCO.2021.39.15_suppl.7513