Efficacy and safety of copanlisib in patients with relapsed or refractory marginal zone lymphoma

Abstract

Marginal zone lymphoma (MZL) is challenging to treat, with many patients relapsing following initial treatment. We report the long-term efficacy and safety of copanlisib, a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, in the subset of 23 patients with relapsed/refractory MZL treated in the phase 2 CHRONOS-1 study (#NCT01660451, Part B; www.clinicaltrials.gov). Patients had a median of 3 prior lines of therapy, including rituximab and alkylating agents, and received IV copanlisib 60 mg on days 1, 8, and 15 of 28-day cycles for a median of 23 weeks. The objective response rate was 78.3% (18/23; 3 complete responses and 15 partial responses). The median duration of response was 17.4 months (median follow-up, 9.4 months), and median time to response was 2.1 months. Median progression-free survival was 24.1 months (median follow-up, 10.3 months), and median overall survival was not reached (median follow-up, 28.4 months). The most common all-grade treatment-emergent adverse events (TEAEs) included fatigue (52.2%, 12/23), diarrhea, and transient, infusion-related hyperglycemia (each 47.8%, 11/23). Nineteen patients (82.6%) had grade 3/4 TEAEs, most commonly transient, infusion-related hyperglycemia and hypertension (each 39.1%, 9/23). TEAEs led to dose reduction or dose interruptions /delays in 9 patients (39.1%) and 18 patients (78.3%), respectively. Patients with activated PI3K/B-cell antigen receptor signaling had improved response rates. Overall, copanlisib demonstrated strong efficacy, with a short time to objective response, improved objective response rate with longer treatment duration, durable responses, and manageable safety, in line with previous reports. These data provide rationale for long-term treatment with copanlisib in patients with relapsed/refractory MZL.

Conflict of interest statement

Conflict-of-interest disclosure: P.P. has received honoraria from Genesis, Gilead, Roche, and Takeda and research support from Genesis, Roche, and Takeda. G.A.F. has received fees for consultancy and lecturing from AbbVie, AstraZeneca, Bayer, Janssen, and Roche. M.Ö. has received research funding from AbbVie, Archigen, Bayer, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Roche, and Takeda; travel support from AbbVie, Abdi İbrahim, Amgen, Bristol Myers Squibb, Janssen, Jazz, Roche, Sanofi, and Takeda; and honoraria from Amgen and Takeda. A.S. has served on speaker bureaus for AbbVie, Amgen, ArQule, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Eisai, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sandoz, Servier, and Takeda; advisory boards for Bayer, Bristol Myers Squibb, Eisai, Gilead, Merck Sharp & Dohme, Pfizer, and Servier; and has received fees for consultancy from ArQule. F.H. is employed by Bayer AG. J.G.-V. is employed by Bayer HealthCare Pharmaceuticals, Inc. B.H.C. is employed by Bayer HealthCare Pharmaceuticals, Inc. P.L.Z. has received fees for consultancy from EUSA Pharma, Merck Sharp & Dohme, Sanofi, and Verastem; has served on speaker bureaus for Bristol Myers Squibb, Celgene, Celltrion, EUSA Pharma, Gilead, Immune Design, Janssen, Kyowa Kirin, Merck Sharp & Dohme, Portola, Roche, Servier, and Verastem; and advisory boards for Bristol Myers Squibb, Celgene, Celltrion, EUSA Pharma, Gilead, Immune Design, Janssen, Kyowa Kirin, Merck Sharp & Dohme, Portola, Roche, Sandoz, Servier, and Verastem. M.D. has received honoraria from Celgene, Janssen, and Roche; has served on scientific advisory boards for Acerta, Bayer, Celgene, Gilead, Janssen, Novartis, Roche, and Sandoz; has received speaker’s honoraria from Bayer, Celgene, Gilead, Janssen, and Roche; and has received institutional support from Celgene, Janssen, and Roche. The remaining authors declare no competing financial interests.

© 2021 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

ORR by histological subtype. Error bars represent 95% CI. MALT, mucosa-associated lymphoid tissue.

Figure 2.

Patient response and efficacy outcomes. (A) Best change in target lesion size by histological subtype. (B) Duration of response. (C) Response in patients achieving a CR or PR. (D) PFS. (E) Overall survival. Median DoR includes censored values for 13 patients, and median PFS includes censored values for 17 patients. The percentage best change in the sum of the diameters of all target lesions from baseline as assessed by the investigator is shown; the best change in target lesion size per the investigator onsite assessment could not be determined in 4 patients. DoR, duration of response; NE, not evaluable; OS, overall survival. *Each bar represents 1 patient.