The phase 2 study of idelalisib monotherapy for indolent non-Hodgkin lymphomas (iNHLs) was completed in 2018; final efficacy and safety data with up to 6.7 years long-term follow-up are reported. ...Patients with iNHL refractory to both rituximab and an alkylating agent were enrolled and received 150 mg idelalisib twice daily (N = 125). Idelalisib resulted in an overall response rate of 57.6% with 34.4% continuing therapy for ≥12 months. The median progression-free survival and duration of response were 11.0 and 11.8 months for follicular lymphoma, 22.2 and 20.4 months for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM), and 6.6 and 18.4 months for marginal zone lymphoma (MZL). Median overall survival after extended follow-up was 48.6 (95% CI 33.9, 71.7) months. Long-term follow-up did not reveal new safety concerns. These data indicate beneficial outcomes with longer follow-up after idelalisib for treatment of iNHL including in patients with LPL/WM and MZL.
A negative interim positron emission tomography/computerized tomography (PET/CT) after 1 to 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with newly diagnosed, ...nonbulky stage I or II Hodgkin lymphoma (HL) predicts a low relapse rate. This phase 2 trial was designed to determine if a population of patients with early-stage disease can be treated with short-course ABVD without radiation therapy (RT) on the basis of a negative interim PET/CT, thereby limiting the risks of treatment. Between 15 May 2010 and 21 February 2013, 164 previously untreated patients with nonbulky stage I/II HL were enrolled, and 149 were included in the final analysis. Patients received 2 cycles of ABVD followed by PET. Deauville scores 1 to 3 were negative (≤ liver uptake) based on central review. PET− patients received 2 more cycles of ABVD, and PET+ patients received 2 cycles of dose-intense bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus 3060-cGy involved-field RT. The primary objective was to determine 3-year progression-free survival (PFS) for the PET− group. One hundred thirty-five patients (91%) were interim PET−, and 14 patients (9%) were PET+. With median follow-up time of 3.8 years, the estimated 3-year PFS was 91% for the PET− group and 66% for the PET+ group (hazard ratio, 3.84; 95% confidence interval, 1.50-9.84; P = .011). There was 1 death as a result of suicide. Four cycles of ABVD resulted in durable remissions for a majority of patients with early-stage nonbulky HL and a negative interim PET. This trial was registered at www.clinicaltrials.gov as #NCT01132807.
•Interim PET− nonbulky stage I/II patients had 3-year PFS of 91% with 4 ABVD cycles and no RT.•Too few patients were interim PET+ to draw firm conclusions about efficacy of escalated BEACOPP plus involved-field RT.
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Atypical response patterns following immune checkpoint blockade (ICB) in Hodgkin lymphoma (HL) led to the concept of continuation of treatment beyond progression (TBP); however, the longitudinal ...benefit of this approach is unclear. We therefore performed a retrospective analysis of 64 patients treated with ICB; 20 who received TBP (TBP cohort) and 44 who stopped ICB at initial progression (non‐TBP cohort). The TBP cohort received ICB for a median of 4.7 months after initial progression and delayed subsequent treatment by a median of 6.6 months. Despite receiving more prior lines of therapy, the TBP cohort achieved longer progression‐free survival with post‐ICB treatment (median, 17.5 months vs. 6.1 months, p = .035) and longer time‐to‐subsequent treatment failure, defined as time from initial ICB progression to failure of subsequent treatment (median, 34.6 months vs. 9.9 months, p = .003). With the limitations of a retrospective study, these results support the clinical benefit of TBP with ICB for selected patients.
To investigate the potential benefit of treatment beyond progression in patients with Hodgkin lymphoma, a multicenter retrospective analysis of 64 patients treated with immune checkpoint blockade was performed. Some patients stopped therapy at initial progression and some received treatment beyond progression. Results are reported here.
Abstract Purpose Lenalidomide and panobinostat have demonstrated single agent efficacy of 14-50% and 27-58%, respectively in Hodgkin lymphoma (HL). This phase I/II study was conducted to determine ...the maximum tolerated dose (MTD), safety, and efficacy of lenalidomide combined with panobinostat in relapsed/refractory HL. Study Design : In the phase 1 trial, previously treated patients with classical or lymphocyte predominant HL received escalating doses of lenalidomide days 1-21 and panobinostat three times a week (TIW) every 28 days. Dose limiting toxicity (DLT) was defined during cycle 1. Once the MTD was determined, a phase 2 study was conducted to determine overall response (OR). Results : Twenty-four patients enrolled; 11 in the phase I and 13 in phase II portions. No DLT were observed but 2 patients receiving 25 mg lenalidomide and 20 mg panobinostat experienced neutropenia and thrombocytopenia > 14 days in cycle 2, leading to selection of 25 mg lenalidomide d1-21 and 15 mg panobinostat TIW for the phase 2 dose. In all 24 patients, grade 3-4 toxicities consisted of neutropenia (58%), thrombocytopenia (42%), lymphopenia (25%), and febrile neutropenia (25%). OR was 16.7% (2 CR and 2 PR). One patient with CR had LP HL and received 22 cycles. Median PFS and OS were 3.8 and 16.4 months, respectively. Conclusion : Although the combination of panobinostat and lenalidomide appears safe in patients with relapsed/refractory HL, the limited efficacy and significant rates of neutropenia and febrile neutropenia observed do not support further evaluation of this combination in HL. This trial was registered at clinicaltrials.gov #NCT01460940.
Compared with solvent-based taxanes, nanoparticle albumin-bound (nab
®
) paclitaxel has demonstrated improved efficacy and tolerability in several solid tumor malignancies. Studies evaluating nab ...paclitaxel in patients with lymphoma are lacking. In this planned phase-I/phase-II study, we sought to determine the safety and efficacy of nab-paclitaxel in patients with relapsed/refractory (R/R) lymphoma. Eligible patients (R/R to ≥2 prior systemic therapies) received weekly nab-paclitaxel on days 1, 8 and 15 every 28 days. Dosing was initiated at 100 mg/m
2
with dose escalations in 25 mg/m
2
increments up to 150 mg/m
2
in a classic 3 + 3 design. Twenty heavily pretreated patients (median 5 prior regimens), including 65% with refractory disease, enrolled. The maximum dose tested was well tolerated and grade 3/4 hematologic adverse events (neutropenia 25%, thrombocytopenia 20% and anemia 15%) were modest. The overall response rate was 10% with two partial responses, leading to a decision to close the study prematurely.
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