Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma

Abstract

This pivotal phase 2 study evaluated the safety and efficacy of brentuximab vedotin in patients with relapsed or refractory (R/R) systemic anaplastic large cell lymphoma (ALCL). After a median observation period of approximately 6 years from first treatment, we examined the durability of remission, progression-free survival (PFS), overall survival (OS), and safety outcomes of patients treated on this trial. Among all enrolled patients (n = 58), no progressions were observed beyond 40 months, and median OS was not reached. Patients with a complete response (CR), as assessed by the investigator (38 of 58, 66%), continued to demonstrate improved outcomes with neither median OS nor PFS reached. Of the 38 CR patients, 16 received a consolidative stem cell transplant (SCT) with median PFS not reached. Among patients who were on-study and in remission at study closure, 16 patients had not received any new treatment after single-agent brentuximab vedotin other than consolidative SCT. Among this subset of 16 patients, 8 received SCT, and the remaining 8 patients (14% of all enrolled patients) remained in sustained remission without consolidative SCT or any new anticancer therapy. Thirty-three patients experienced peripheral neuropathy, among whom, the majority (30 of 33, 91%) had experienced resolution or improvement at their last assessment. These final results, which demonstrated a high rate of peripheral neuropathy resolution, and durable remissions in a subset of patients with relapsed or refractory systemic ALCL, provide evidence that single-agent brentuximab vedotin may be a potentially curative treatment option. This trial was registered at www.clinicaltrials.gov as #NCT00866047.

Conflict of interest statement

Conflict-of-interest disclosure: J.M.P., K.F., and D.A.K. are employees of and have equity ownership of Seattle Genetics. D.H. is an employee of and has equity ownership of Takeda. P.B. received funding from Seattle Genetics and Takeda. J.M.C. received funding from Seattle Genetics, Takeda, Roche, and Bristol-Myers Squibb. B.P., M.F., T.I., J.M., J.D.R., A.S., and R.R. received funding from Seattle Genetics; R.A. received funding from Kura, Celgene, Genentech, Infinity, Seattle Genetics, Agensys, Bristol-Myers Squibb, Merck, Millennium, Regeneron, Janssen, and Pharmacyclics. N.L.B. received funding from Celgene, Seattle Genetics, Genentech, Pfizer, KITE, Merck, Bristol-Myers Squibb, Immune Design, Forty Seven, Affimed, Janssen, Pharmacyclics, Millennium, AstraZeneca, ImaginAb, and Novartis. B.P. and T.I. received honoraria from Takeda. P.B. received honoraria from Takeda, Roche, Gilead, and Bristol-Myers Squibb. M.F. received honoraria from Seattle Genetics. M.F. and R.R. has received consultant fees from Seattle Genetics. T.I. has received consultant fees from Seattle Genetics and Takeda. J.M. has received consultant fees from Celgene. B.P. has received consultant fees from Seattle Genetics. N.L.B. has received consultant fees from Seattle Genetics, KITE, and Gilead. R.A. has received consultant fees from NanoString Technologies, Pharmacyclics, Spectrum, Bristol-Myers Squibb, Forty Seven, Sutro Biopharma, Juno Therapeutics, and Gilead. J.M. is a member of the speakers bureau for Seattle Genetics and Celgene. M.F., B.P., and R.R. have received travel expenses from Seattle Genetics.

© 2017 by The American Society of Hematology.

Figures

Figure 1.

End-of-study OS and PFS in patients with relapsed or refractory systemic ALCL treated with brentuximab vedotin. OS and PFS per investigator assessment were analyzed using Kaplan-Meier methodology. Median observation time was 6 years from the start of treatment. Patients were observed for a median of 5 years after the end of treatment. (A) OS for all patients. (B) OS by best response. (C) PFS for all patients. (D) PFS by best response.

Figure 2.

OS and PFS by ALK status. End-of-study (A) OS and (B) PFS were comparable among patients with ALK+ and ALK– systemic ALCL.

Figure 3.

OS and PFS by SCT status. End-of-study (A) OS and (B) PFS in patients with a best response of CR subset by receipt of consolidative SCT.

Figure 4.

Patients who were in remission and in follow-up at study closure. Includes patients who were in remission according to the investigator and on-study at the time of study closure. Patients are shaded according to ALK status. A consolidative SCT was performed in 8 patients, and 8 patients received no further therapy after completing brentuximab vedotin. Allo-SCT, allogeneic SCT; Auto-SCT, autologous SCT; EOS, end of study.