Allogeneic CAR-T Yields Some Responses in Multiple Myeloma After Anti-BCMA Therapy

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The best response was very good partial response in 3 of 5 participants.

Bhagirathbhai Dholaria, MD

Bhagirathbhai Dholaria, MD

Allogeneic P-BCMA-ALLO1 chimeric antigen receptor (CAR) T-cell therapy yielded some responses in patients with relapsed/refractory multiple myeloma whose disease had progressed after prior BCMA-targeted therapy.1

These data, from a phase 1 trial, were presented at the American Association for Cancer Research (AACR) Annual Meeting 2024, held on April 5-10, 2024, in San Diego, California, by Bhagirathbhai Dholaria, MD, Associate Professor of Medicine (Hematology/Oncology), Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

"Multiple myeloma remains incurable, and patients often relapse, despite initial high response rates with BCMA-targeted immunotherapies, including autologous CAR-T therapies," Dholaria said in a statement."New treatment options are urgently needed for these patients, which is why I'm encouraged by these impressive Phase 1 subgroup results, which may be the first report of an allogeneic CAR-T therapy showing clinical activity in heavily pretreated patients whose myeloma has progressed after multiple BCMA-targeted immunotherapies."

The data are from 5 patients who were treated with P-BCMA-ALLO1 after having progressed on BCMA targeting CAR T-cell therapy, T-cell engagers, or both. Patients received between 2 X 106 and 6 X 106 cells/kg of P-BCMA-ALLO1 with lymphodepletion regimens of either 500 mg/m2 cyclophosphamide plus 30 mg/m2 X 3 days fludarabine (n = 2), or 1000 mg/m2 cyclophosphamide plus 30 mg/m2 X 3 days fludarabine (n = 3).1

The 5 participants had a median age of 62 years and a median of 10 prior lines of therapy. Two had received prior teclistamab, 2 had received prior CAR-T and 1 had received prior teclistamab and CAR-T.1

Dholaria and colleagues found that P-BCMA-ALLO1 was well tolerated with no dose limiting toxicities or cases of graft versus host disease. Three participants developed cytokine release syndrome (grade 2) and 1 developed grade 2 immune effector cell neurotoxicity syndrome. Three participants (60%) had a response with a best response of very good partial response (VGPR). The 2 participants who did not respond had previously received and failed to achieve clinical response with teclistamab. One participant who achieved a VGPR had previously received both teclistamab and CAR T-cell therapy.1

"These new data build on the P-BCMA-ALLO1 data presented at ASH 2023, which demonstrated a 100% overall response rate in patients who had not been previously treated with a BCMA-targeted therapy. The new findings also provide additional evidence that our investigational, off-the-shelf allogeneic CAR-T therapy could be an appropriate treatment for a broader range of patients with multiple myeloma, including those with relapsed/refractory disease whose cancer progressed following prior BCMA-targeted therapy, representing the highest unmet need in this setting," Syed Rizvi, MD, Chief Medical Officer, Poseida, added.2 "In addition, we continue to explore the optimal lymphodepletion regimen for CAR-T in solid tumors and are directly applying these learnings to our P-MUC1C-ALLO1 trial with the goal of delivering the same benefits in solid tumors as we have seen in myeloma. We look forward to sharing more fulsome datasets on both our BCMA and MUC1-C programs in the second half of 2024."

REFERENCES
1. Dholaria B, Shune L, Kin A, et al. Clinical activity of P-BCMA-ALLO1, a B-cell maturation antigen (BCMA) targeted allogeneic chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed refractory multiple myeloma (RRMM) patients (pts) following progression on prior BCMA targeting therapy. Presented at: AACR Annual Meeting 2024; April 5-10; San Diego, California. Poster CT071 / 21
2. Poseida Therapeutics Presents New Phase 1 Data at AACR 2024 Supporting Potential of P-BCMA-ALLO1 Allogeneic CAR-T Therapy to Benefit Broad Range of Patients with Multiple Myeloma. News release. Poseida Therapeutics. April 8, 2024. https://www.prnewswire.com/news-releases/poseida-therapeutics-presents-new-phase-1-data-at-aacr-2024-supporting-potential-of-p-bcma-allo1-allogeneic-car-t-therapy-to-benefit-broad-range-of-patients-with-multiple-myeloma-302110563.html
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