Ciltacabtagene Autoleucel, an Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up

Author(s): Thomas Martin, MD¹; Saad Z. Usmani, MD²; Jesus G. Berdeja, MD³; Mounzer Agha, MD⁴; Adam D. Cohen, MD⁵; Parameswaran Hari, MD⁶; David Avigan, MD⁷; Abhinav Deol, MD⁸; Myo Htut, MD⁹; Alexander Lesokhin, MD²; Nikhil C. Munshi, MD^10,11; Elizabeth O’Donnell, MD¹²; A. Keith Stewart, MBChB¹³; Jordan M. Schecter, MD¹⁴; Jenna D. Goldberg, MD¹⁴; Carolyn C. Jackson, MD, MPH¹⁴; Tzu-Min Yeh, MS¹⁴; Arnob Banerjee, MD¹⁵; Alicia Allred, PhD¹⁵; Enrique Zudaire, PhD¹⁵; William Deraedt, MSc¹⁶; Yunsi Olyslager, MSc¹⁶; Changwei Zhou, PhD¹⁷; Lida Pacaud, MD¹⁷; Deepu Madduri, MD¹⁴; Andrzej Jakubowiak, MD¹⁸; Yi Lin, MD, PhD¹⁹; and Sundar Jagannath, MD²⁰

Source: DOI: 10.1200/JCO.22.00842 Journal of Clinical Oncology 41, no. 6 (February 20, 2023) 1265-1274.

Dr. Maen Hussein's Thoughts

CAR-T for myeloma, impressive response rate, overall survival not reached.

PURPOSE

CARTITUDE-1, a phase Ib/II study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel) in heavily pretreated patients with relapsed/refractory multiple myeloma, yielded early, deep, and durable responses at 12 months. Here, we present updated results 2 years after last patient in (median follow-up [MFU] approximately 28 months), including analyses of high-risk patient subgroups.

METHODS

Eligible patients had relapsed/refractory multiple myeloma, had received ≥ 3 prior lines of therapy or were double refractory to a proteasome inhibitor and immunomodulatory drug and had received prior proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy. Patients received a single cilta-cel infusion 5-7 days after lymphodepletion. Responses were assessed by an independent review committee.

RESULTS

At a MFU of 27.7 months (N = 97), the overall response rate was 97.9% (95% CI, 92.7 to 99.7); 82.5% (95% CI, 73.4 to 89.4) of patients achieved a stringent complete response. Median duration of response was not estimable. Median progression-free survival (PFS) and overall survival (OS) were not reached; 27-month PFS and OS rates were 54.9% (95% CI, 44.0 to 64.6) and 70.4% (95% CI, 60.1 to 78.6), respectively. Overall response rates were high across all subgroups (95.1%-100%). Duration of response, PFS, and/or OS were shorter in patients with high-risk cytogenetics, International Staging System stage III, high tumor burden, or plasmacytomas. The safety profile was manageable with no new cilta-cel–related cytokine release syndrome and one new case of parkinsonism (day 914 after cilta-cel) since the last report.

CONCLUSION

At approximately 28 months MFU, patients treated with cilta-cel maintained deep and durable responses, observed in both standard and high-risk subgroups. The risk/benefit profile of cilta-cel remained favorable with longer follow-up.

Author Affiliations

¹UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA;²Memorial Sloan Kettering Cancer Center, New York, NY;³Sarah Cannon Research Institute, Nashville, TN;⁴UPMC Hillman Cancer Center, Pittsburgh, PA;⁵Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA;⁶Medical College of Wisconsin, Milwaukee, WI;⁷Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;⁸Karmanos Cancer Institute, Wayne State University, Detroit, MI;⁹City of Hope Comprehensive Cancer Center, Duarte, CA;¹⁰Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;¹¹VA Boston Healthcare System, West Roxbury, MA;¹²Massachusetts General Hospital, Harvard Medical School, Boston, MA;¹³University Health Network and the Princess Margaret Cancer Centre, Toronto, ON, Canada;¹⁴Janssen R&D, Raritan, NJ;¹⁵Janssen R&D, Spring House, PA;¹⁶Janssen R&D, Beerse, Belgium;¹⁷Legend Biotech, Inc, Piscataway, NJ;¹⁸University of Chicago, Chicago, IL;¹⁹Mayo Clinic, Rochester, MN;²⁰Mount Sinai Medical Center, New York, NY

Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM).

Triplet second line therapy shows superiority over daratumumab bortezomib and dexamethasone. This regimen is now used in first line with lenalidomide in some patients as quadruplet therapy, hence this second line regimen with Blantamab could be a second line option. The eye exam is still a pain and it is also more toxic.

Teclistamab in Relapsed or Refractory Multiple Myeloma

The Bi-specific antibody era has started full-force with impressive results and reasonable toxicities, in different hematological neoplasms. Community oncology adoption of Bi-specific antibody will be successful, once standard operating procedures are in place, and multidisciplinary training takes place insofar as management of CRS. I am optimistic as to the uptake of this class of drugs in 1-2 years, pending payer coverage issues.

Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA

MRD status in MM has unquestionable prognostic informational value, however many questions remain as how to address positive / negative MRD results. Should we de-escalate or stop Rx? When? Can we escalate Rx if + MRD? Which regimen, how long? It will be another few years till objective data are available. I do see value in at least having identification of clonality established upfront for tracking.