Indolent B-cell lymphoma
The role of idelalisib as monotherapy in relapsed iNHL was investigated in a Phase II study involving 125 patients from April 2011 to October 2012. Subtypes of iNHL included were FL (n=72), SLL (n=28), marginal-zone lymphoma (n=15), and lymphoplasmacytic lymphoma (n=10). Eligible patients were considered refractory to treatment with both rituximab and an alkylating agent. ORR was 57%. Response rates were comparable within the subgroups of iNHL (ORR: 47%–80%). The median duration of response was 12.5 months, and the median PFS duration was 11 months. Median OS was 20.3 months with 80% OS at the end of the study (Table 1).27
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SAFETY AND ADVERSE EVENTS
The adverse effects (AE) associated with idelalisib combining the three most recent clinical trials are summarized in Table 2. In the relapsed CLL trial, the most common AE in the idelalisib + R treatment group were fatigue (24%), nausea (24%), diarrhea (19%), fever (29%), and chills (22%). Serious adverse effects (SAE) included pneumonia (6%), febrile neutropenia (5%), diarrhea (3%), pyrexia (6%), and dyspnea (1%). Laboratory abnormalities included elevation in alanine transaminase/aspartate transaminase, which mostly occurred within the first 12 weeks of treatment. Others include anemia, neutropenia, and thrombocytopenia. In addition, lymphocytosis, which is an observed class effect of BCR pathway inhibitors, was seen.23 Idelalisib-associated lymphocytosis peaked at week 2 and resolved by week 12; however, in combination with rituximab, idelalisib did not show prominent lymphocytosis.24
(To view a larger version of Table 2, click here.)
In the relapsed/refractory iNHL trial, the most common AE with idelalisib monotherapy included diarrhea (13%) and pneumonia (7%). Dose reduction from 150 mg BID to 100 mg BID was necessary in 34% of patients due to AE (hepatotoxicity, colitis, and pneumonitis/pneumonia).27
In the treatment-naïve CLL trial, SAE were higher with diarrhea/colitis at 42.2% and pneumonia at 18.8%, presumably reflecting a more intact immune system.25
Idelalisib prescribing information provides a black box warning for serious and/or fatal toxicities. These included grade ≥3 diarrhea/colitis (14%), hepatotoxicity (14%), pneumonitis, and intestinal perforation. In the setting of SAE, idelalisib is withheld until resolution of AE, and then dose reduction to 100 mg BID is recommended. Recurrence of AE after dose reduction or occurrence of a life-threatening AE warrants permanent treatment discontinuation. Corticosteroids are recommended for treatment of severe colitis/pneumonitis.28
