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Long-Term Efficacy & Safety of Copanlisib for Indolent B-Cell Lymphoma

Nalley, Catlin

doi: 10.1097/01.COT.0000553150.03309.9a
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indolent B-cell lymphoma

indolent B-cell lymphoma

SAN DIEGO—Treatment with the PI3K inhibitor copanlisib has demonstrated durable responses and a manageable safety profile among patients with relapsed or refractory indolent B-cell lymphoma (J Clin Oncol 2017;35(35):3898-3905).

This data from the CHRONOS-1 study showed an objective response rate of 59 percent and, unlike oral PI3K inhibitors, “there was a low incidence of severe adverse events, such as pneumonitis and colitis, with copanlisib—possibly due to IV dosing and intermittent dose schedule,” according to the researchers.

Given late-onset reports of severe toxicities related to ongoing use of some oral PI3K inhibitors, a 2-year follow-up of the efficacy and safety from CHRONOS-1 was conducted. Findings from this follow-up were recently presented at the 2018 ASH Annual Meeting (Abstract 1595).

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Study Methodology

Eligible patients included those with histologically confirmed indolent B-cell non-Hodgkin lymphoma (follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma, and lymphoplasmacytoid/Waldenström macroglobulinemia) who had relapsed after, or were refractory to, ≥2 prior lines of treatment. Prior treatment had to include rituximab and an alkylating agent or regimen, according to investigators.

Patients received copanlisib at a fixed dose of 60 mg via 1-hour IV infusion on days 1, 8, and 15 of a 28-day cycle. This treatment continued until disease progression or unacceptable toxicity.

Objective response rate (ORR) after ≥4 cycles as assessed per independent radiologic review was the primary efficacy endpoint. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were secondary efficacy endpoints. Adverse events were reported using MedDRA (version 19.1), according to study authors.

The team enrolled the last patient in February 2016 and the initial data cutoff was June 2016. For long-term follow-up, the data cutoff was February 2018.

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Key Findings

ASH 2018 Abstract 1595

The CHRONOS-1 study treated a total of 142 patients. Patient demographics, included:

  • Predominant histologies: FL (n=104) and MZL (n=23)
  • Median age: 63 years (range 25-82)
  • Median number of prior lines of treatment: 3 (range 2-9)
  • Sixty-one percent of patients were refractory to their previous treatment regimen.

As of February 2018, the median duration of treatment was 6.0 months (range 0.2-44). Researchers reported an ORR of 60.6 percent. Twenty-four patients had a complete response (CR); 21 were in the FL group and three with MZL. Investigators reported that “the 24 CRs represent an increase of seven compared to the original primary analysis.”

Data showed a median DOR of 14.1 months (95% CI 8.3; 22.3). “With 72 events, the median PFS was 12.5 months (95% CI 9.0; 18.4) and, with a total of 52 events, the median OS was 42.6 months (95% CI 36.5; not reached),” according to the researchers.

Eleven patients (9 FL, 2 MZL) remained on treatment (range 24.8-43.9 months) at the data cutoff. Thirty-eight patients (26.8%) discontinued treatment due an adverse event (AE) not associated with disease progression.

Dose reductions or dose interruptions were recorded in 36 (25.4%) and 72 (50.7%) patients, respectively, due to treatment-related AEs. “With a median safety follow-up of 6.7 months, the most common treatment-emergent AEs (all-grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7%) and transient hypertension (29.6%/23.9% G3),” according to the findings.

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Implications, Commentary

This long-term follow-up shows that there is a durable response and manageable safety profile associated with the use of copanlisib in this patient population.

“Analysis of the 2-year follow-up of patients with relapsed or refractory indolent B-cell lymphoma treated with copanlisib demonstrated a deepening of the responses with a conversion of seven patients from PR to CR, durable responses, and manageable AEs,” study authors concluded. “Moreover, the benefit/risk ratio for copanlisib treatment remains favorable with no evidence of worsening of AEs for patients treated long-term.”

Commenting on the study, Pallawi Torka, MD, Assistant Professor of Oncology, Lymphoma & Myeloma Division, Department of Medicine, Roswell Park Comprehensive Cancer Center, said: “Long-term follow-up of patients with low-grade lymphoma on copanlisib in the CHRONOS-1 study shows improving responses with no new safety concerns, which is reassuring.

“It is surprising, however, that 1 in 4 patients discontinued the drug due to reasons other than disease progression, especially since both hyperglycemia and hypertension, the two major side effects of copanlisib, are easily treatable and should not really necessitate stopping the drug. I look forward to the full dataset to clarify this issue.”

Catlin Nalley is associate editor.

Wolters Kluwer Health, Inc. All rights reserved.
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