Phase 2 Data for Tisagenlecleucel, Tafasitamab Show Objective Responses in More Than Half of Patients

Earlier this month, drugmakers unveiled positive new phase 2 data for a pair of therapies targeting 2 types of non-Hodgkin lymphomas.

The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah) had an overall response rate (ORR) of nearly 90% among patients with relapsed or refractory follicular lymphoma, and the humanized Fc-modified cytolytic CD19-targeting monoclonal antibody tafasitamab (Monjuvi) had an ORR of more than 50% when administered in combination with lenalidomide (Revlimid) to patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Both sets of data were unveiled at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, which was held earlier this month in a virtual format.

Novartis AG released the pivotal phase 2 data from its ELARA trial, showing tisagenlecleucel led to an ORR of 86% (95% CI, 78-92) in patients with follicular lymphoma, and a 66% complete response (CR) rate (95% CI, 56-75).¹ None of the 97 patients evaluated for safety experienced grade 3 or 4 cytokine release syndrome (CNS), the most common adverse event associated with CAR T-cell therapies, though nearly half (49%) had grade 1 or 2 CNS.

“Our goal as researchers is to continue to explore the potential of CAR-T therapy, and the robust ELARA safety and efficacy findings suggest Kymriah may play an important role in the third-line treatment of relapsed or refractory follicular lymphoma,” said Stephen J. Schuster, MD, of the University of Pennsylvania’s Perelman School of Medicine, in a press release.²

The ELARA trial had a median follow-up of 11 months, by which time the duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were not reached. Schuster and colleagues estimated DOR for patients with CR at six months to be 94% (95% CI, 82-98) and 76% for patients with PFS at six months (95% CI, 65-84). The median number of prior therapies in the cohort was 4, though the range went from 2-13 prior therapies.

Nine percent of patients reported grade 1 or 2 neurological events, and 1 patient had a grade 4 neurological event, though all recovered. The most common grade 3 or higher adverse events in the first 8 weeks following infusion were neutropenia (28%) and anemia (13%). No treatment-related deaths were reported.

Novartis said it is committed to expanding the availability of CAR T-cell therapies, and will push forward with regulatory submissions for the indication as soon as possible.

Tafasitamab results. Meanwhile, Incyte Corp. and MorphoSys US Inc. said its phase 2 L-MIND trial showed tafasitamab had an ORR of 57.5% (46 out of 80 patients; 95% CI, 45.9-68.5) when given to patients with relapsed or refractory DLBCL in combination with lenalidomide.³ Forty percent of patients achieved CR, and the median duration of response was 43.9 months (95% CI, 26.1 - not reached) The median OS was 33.5 months (95% CI, 18.3 - not reached) and the median PFS was 11.6 months (95% CI, 6.3-45.7).

“The three-year follow-up data not only show a durable response and consistent safety profile in patients with relapsed or refractory DLBCL treated with tafasitamab plus lenalidomide, it also suggests the combination could potentially lead to durable remission,” said MorphoSys senior vice president Nuwan Kurukulasuriya, in a press release.⁴ “We are looking forward to sharing these long-term follow-up findings with the scientific community.”

Tafasitamab in combination with lenalidomide was approved by the Food and Drug Administration via its accelerated approval pathway last July for the treatment in adult patients with relapsed or refractory DLBCL not otherwise specified, including those arising from low-grade lymphoma, who are not eligible for autologous stem cell transplantation.

References

1. Schuster SJ, Dickinson MJ, Dreyling MH, et al. Efficacy and safety of tisagenlecleucel (Tisa-cel) in adult patients (Pts) with relapsed/refractory follicular lymphoma (r/r FL): Primary analysis of the phase 2 Elara trial. J Clin Oncol. 2021;39(Suppl 15): abstr 7508. doi:10.1200/JCO.2021.39.15_suppl.7508
2. Novartis’ Kymriah pivotal trial demonstrates strong response rates and remarkable safety profile in relapsed or refractory follicular lymphoma. News release. Novartis; June 2, 2021. Accessed June 19, 2021. https://www.novartis.com/news/media-releases/novartis-kymriah-pivotal-trial-demonstrates-strong-response-rates-and-remarkable-safety-profile-relapsed-or-refractory-follicular-lymphoma
3. Düll J, Maddocks KL, 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. 2021;39(Suppl 15): abstr 7513. doi:10.1200/JCO.2021.39.15_suppl.7513
4. Incyte and MorphoSys announce three-year results from phase 2 L-MIND study of tafasitamab in combination with lenalidomide for the treatment of relapsed or refractory DLBCL. News release. BusinessWire; June 4, 2021. Accessed June 19, 2021. https://www.businesswire.com/news/home/20210604005569/en/Incyte-and-MorphoSys-Announce-Three-Year-Results-from-Phase-2-L-MIND-Study-of-Tafasitamab-in-Combination-with-Lenalidomide-for-the-Treatment-of-Relapsed-or-Refractory-DLBCL