This month, in a Letter to the Editor of Haematologica, Professor Gilles Salles, from Hospices Civils de Lyon, University Claude Bernard, Pierre Benite, France, and colleagues published the findings of their post-hoc subgroup analysis 1of patients with FL (grade 1, 2, or 3a) enrolled in the phase II DELTA study of idelalisib monotherapy for R/R iNHL ( NCT01282424).
The DELTA studyfound that 150mg idelalisib twice daily showed anti-tumor activity and was tolerated well across four histologic subtypes of iNHL (n = 125), including 72 FL patients (58%). 2The current post-hoc subgroup analysis was performed to understand further the safety and anti-lymphoma effect of idelalisib monotherapy specifically in refractory FL patients.
- ORR = 55.6% (40/72; 95% CI, 43.4–67.3; P<0.001); did not differ when stratified grade
- CR = 13.9% (10 pts); PR = 41.7% (30 pts); SD = 31.9% (23 pts); PD = 11.1% (8 pts); overall disease control rate = 87.5%; 1 patient was not evaluable
- ≥50% reduction in the sum of the products of the diameters of the index lymph node reported in 57% of pts
- Median PFS = 11.0 months (95% CI, 8.0–14.0); at 12-months 43.0% of pts were progression-free
- Median OS = not reached; at 24 months, estimated OS = 69.8%; all pts achieving CR had survived
- PD led to discontinuation in 38 pts; 23 initiated another treatment within 1–131 days; 10/38 died
- Idelalisib was discontinued in 22 pts for a reason other than PD or death; 13 pts initiated their next treatment within 8–439 days; 4 pts subsequently died
- Median duration of idelalisib exposure = 6.5 (0.6–31.0) months
- The most common ≥Grade 3 TEAEs = Diarrhea (13.9%), pneumonia (6.9%), and pyrexia (4.2%)
- The most frequent ≥Grade 3 laboratory abnormalities = neutropenia (22.2%) and alanine aminotransferase/aspartate aminotransferase elevations (13.9%)
- SAEs = pyrexia (12.5%), diarrhea (6.9%), pneumonia (5.6%), and colitis (4.2%)
- Bleeding events of any grade reported in 9 pts; 3 pts had ≥Grade 3 events; all bleeding events resolved without a change in dose
- Neutropenia of any grade reported in 37 pts; 16 pts had ≥Grade 3
- Upper respiratory infections in 11 pts (15.3%) and pneumonia in 8 pts (11.1%) pts; Grade 3 pneumonia reported in 5 pts (6.9%)
- ≥Grade 3 diarrhea or colitis reported in 10 and 2 pts, respectively; idelalisib interrupted and re-challenged in 5 pts of which 4 did not experience a recurrence
- Two pts died from AEs considered possibly (acute cardiac arrest) or probably (drug-induced pneumonitis) related to idelalisib treatment
- Idelalisib treatment was interrupted in 32 patients (44.4%), mainly due to AEs (n=24)
- Dose reduction took place for 22 pts (30.6%); due to AEs (n=21)
- AEs leading to discontinuation of idelalisib reported in 18 pts
Overall, the authors stated that idelalisib monotherapy was effective and consistent regardless of patient age, disease grade, and number of previous treatments. They also went on to state that idelalisib monotherapy had an acceptable and manageable safety profile in heavily pretreated patients with R/R FL.
In addition, it was noted that the rates of cytomegalovirus and Pneumocystis jiroveciiinfection were low (1.3% and 0%, respectively), however stressed that “appropriate monitoring and prophylaxis are still recommended based on recent safety data”. The authors concluded that due to the unmet need in high-risk R/R FL patients, “the overall benefit of idelalisib outweighs these safety concerns”.