Syed Abutalib, MD
Here is the final installment of selected abstracts from the proceedings of the 2015 American Society of Hematology (ASH) Annual Meeting and Exposition, focusing on Hodgkin lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. For other selected abstracts from this conference, see the December 25, 2015; February 10, 2016; and February 25, 2016, issues of The ASCO Post. For full details of these study abstracts, visit https://ash.confex.com/ash/2015/webprogram/start.html.
Abstract 587: Brentuximab vedotin in combination with dacarbazine or bendamustine for frontline treatment of Hodgkin lymphoma in patients aged ≥ 60 years: Interim results of a multicohort phase II study1
Question Asked: What are the efficacy and durability of response to brentuximab vedotin (Adcetris) as monotherapy and in combination?
Abstract Conclusion: Sixty patients have been treated (27 with monotherapy, 22 with the dacarbazine combination, and 11 with the bendamustine [Bendeka, Treanda] combination). Median age for all patients was 76 years (range, 62–92), and 70% were deemed ineligible for conventional chemotherapy.
For patients treated with the dacarbazine combination, the overall response rate was 100% (62% complete responses). The median progression-free survival has not been reached (median observation time, 9.8 months), and 18 of 21 patients remain alive without progressive disease. For patients treated with the bendamustine combination, the starting dose of bendamustine was reduced from 90 to 70 mg/m2 to improve tolerability. The overall response rate was 100% (78% complete response) in the first nine patients; with limited observation time (median, 3.6 months), eight of nine patients remain alive without progressive disease. Treatment-related adverse effects ≥ grade III occurred in 43% of patients overall, severe adverse events were reported for 22% overall, and no patient died within 30 days of the last dose.
Abstract 579: Advanced stage HL patients with a negative PET-scan following treatment with ABVD have excellent outcomes without the need for consolidative radiotherapy regardless of disease bulk at diagnosis2
Questions Asked: Do all patients with advanced HL (defined here as stage I bulky [> 10 cm], stage II with B symptoms and/or bulky disease, and all stage III/IV disease) require consolidation radiation therapy after completion of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine)? Can the end-of-chemotherapy PET (positron-emission tomography) scan guide the decision about consolidative radiotherapy in bulky mediastinal lymphadenopathy?
Abstract Conclusion: In this retrospective analysis, a total of 316 patients met the inclusion criteria. About 62% of the patients had bulky disease. At the end of treatment, 264 (83.5%) patients (none of whom received radiotherapy) were PET-negative (indeterminate n = 4), and 52 (16.5%) patients (79% of whom received consolidative radiotherapy [30–35 Gy]) were PET-positive.
Overall, patients with a PET-negative scan post chemotherapy had a superior 5-year freedom from treatment failure vs those with a PET-positive scan (89% vs 56%, P < .00001). In the PET-negative cohort, there was no difference in outcome comparing the bulky (n = 112) and nonbulky (n = 152) subgroups (5-year freedom from treatment failure of 89% vs 88.5%, P = .50, respectively; 5-year overall survival of 96% vs 94%, P = .51). Similar survival estimates were observed when the analysis was restricted to the 102 PET-negative cases with a bulky mediastinal mass at diagnosis (5-year freedom from treatment failure of 89%; 5-year overall survival of 96%).
Of the 41 PET-positive patients who were able to receive consolidative radiotherapy, the 5-year freedom from treatment failure was 60%, and the 5-year overall survival was 94%.
For the 29 patients with mediastinal PET-positive disease who received radiotherapy (72% with bulky disease at diagnosis), the 5-year freedom from treatment failure was 69.5%.
Abstract 586: The combination of brentuximab vedotin and bendamustine demonstrates marked activity in heavily treated patients with relapsed or refractory Hodgkin lymphoma and anaplastic large T-cell lymphoma: Results of an international multicenter phase I/II experience3
Question Asked: Is this combination treatment safe and efficacious?
Abstract Conclusion: About 36 patients were evaluable for response. The overall response rate was 67%, with 7 patients (19%) attaining a complete response. Eight patients had stable disease. Among the 11 patients who received prior brentuximab vedotin, 6 responded (55%; 2 complete responses, 4 partial responses, 3 with stable disease, 2 with progressive disease). Of the four patients who had prior bendamustine, two had a partial response, one had stable disease, and one had progressive disease). Two patients had received both brentuximab vedotin and bendamustine as single agents prior to initiation of the study: One patient achieved a partial response, and the other experienced progressive disease. The patient with anaplastic large T-cell lymphoma achieved a partial response. The median number of prior systemic therapies was 5 (range, 1–16), with 26 patients having had autologous hematopoietic cell transplantation and 14 patients having received radiation therapy. The observed grade 3–4 toxicities were neutropenia (14%) and pneumonia (14%). (Also refer to abstract 3982.4)
Abstract 581: Remarkable clinical efficacy, hematopoietic cell mobilization activity, and good toxicity profile of the novel BGV regimen (bendamustine, gemcitabine, and vinorelbine) used as salvage therapy prior to autologous hematopoietic cell transplant for relapsed/refractory Hodgkin lymphoma5
Question Asked: Is the bendamustine, gemcitabine, and vinorelbine (BGV) regimen efficacious as second-line therapy? What is its toxicity profile?
Abstract Conclusion: Of 59 enrolled patients, 43 (73%) achieved a complete response and 6 (10%) achieved a partial response, for an objective response rate of 83%. One patient (2%) showed stable disease, whereas eight patients (14%) progressed, and one patient (2%) was not evaluable for response. Among the 49 responding patients, 43 (88%) proceeded to autologous hematopoietic cell transplantation (38 of 43 in complete response, and five of six in partial response).
Abstract 470: Ibrutinib plus rituximab in treatment-naive patients with follicular lymphoma: Results from a multicenter, phase 2 study (PCYC-1125-CA)6
Question Asked: What was the objective response rate to ibrutinib (Imbruvica) combined with rituximab (Rituxan)?
Abstract Conclusion: The mean duration of treatment on ibrutinib was 9.2 months. At a median follow-up of 10.2 months (range, 1.2–16.2), the investigator-assessed objective response rate was 82% (95% confidence interval [CI]: 70.1%–89.4%), with a complete response rate of 27% and a partial response rate of 55% in all treated patients. The median time to best response was 2.7 months (range, 1.1–8.3). Severe adverse events occurred in 13% of patients (12% grade 3 or 4). Atrial fibrillation ≥ grade 3 occurred one patient.
Diffuse Large B-Cell Lymphoma
Abstract 815: Early treatment intensification with R-ICE chemotherapy followed by autologous hematopoietic cell transplantation using yttrium-90-ibritumomab tiuxetan-BEAM for patients with poor risk diffuse large B-cell lymphoma as identified by interim PET/CT scan performed after four cycles of R-CHOP-14: A multicenter phase II study of the Australasian Leukaemia Lymphoma Study Group (ALLG)7
Question Asked: In patients with PET/CT (computed tomography) positivity after four cycles, does early treatment intensification result in 2-year progression-free survival that is equivalent to those who are PET/CT-negative after four cycles treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alone?
Abstract Conclusion: Of the 143 patients with interim PET/CT enrolled from 20 Australian centers, 101 (71%) were deemed PET/CT-negative and 42 (29%) were PET/CT-positive after four cycles. Patients who were PET/CT-negative then received two additional cycles of R-CHOP plus two doses of rituximab. Patients who were PET/CT-positive received three cycles of R-ICE followed by autologous hematopoietic cell transplantation using yttrium-90-ibritumomab tiuxetan-BEAM. Interestingly, the baseline characteristics were comparable between both groups. Of the 101 patients who were PET/CT-negative after four cycles, 5 failed to complete therapy due to progressive disease (3), toxicity (1), or infection (1). Of the 42 patients who were PET/CT-positive after four cycles, 10 failed to complete intensification therapy due to progressive disease (6), second malignancy (1), or consent withdrawal (3). Among those who were PET/CT-positive after four cycles and later underwent autologous hematopoietic cell transplantation, there was one treatment-related death due to viral infection.
At a median follow-up of 35 months, the Kaplan-Meier estimate of 2-year progression-free survival and overall survival for the entire eligible cohort of 151 patients was 72% and 85%, respectively. For the 101 patients who were PET/CT-negative after four cycles and the 42 who were PET/CT-positive after four cycles, 2-year progression-free survival was 74% and 67% (P = .32), and 2-year overall survival was 88% and 78% (P = .11), respectively.
Abstract 814: Brentuximab vedotin with R-CHOP as frontline therapy in patients with high-intermediate/high-risk diffuse large B-cell lymphoma: Results from an ongoing phase II study8
Questions Asked: What was the tolerability of each regimen? What was the complete response rate at the end of treatment?
Abstract Conclusion: Twenty-nine patients were treated with 1.2 mg/kg of brentuximab vedotin and R-CHOP, and 22 patients were treated with 1.8 mg/kg of brentuximab vedotin and R-CHOP. Adverse events in ≥ 50% of patients included peripheral sensory neuropathy (63%), fatigue (61%), nausea (55%), and diarrhea (53%). Grade 3 or higher events occurred in 76% of patients, with the most frequent being neutropenia (33%) and febrile neutropenia (31%). The PET-negative complete response rate was 69% overall; CD30-positive patients had a complete response rate of 76% (19 of 25) vs 63% (12 of 19) in CD30-negative patients by immunohistochemistry. Although progression-free survival data are still immature (median follow-up of 8 months), the estimated progression-free survival rate at 12 months was 82% (95% CI: 58%–93%) in CD30-positive patients and 56% (95% CI: 32%–75%) in CD30-negative patients. Sixty percent (3 of 5) of patients with CD30-negative ABC subtype diffuse large B-cell lymphoma progressed vs 27% (3 of 11) of patients with CD30-positive ABC subtype diffuse large B-cell lymphoma.
Chronic Lymphocytic Leukemia
Late Breaking Abstract: Idelalisib plus bendamustine and rituximab (BR) is superior to BR alone in patients with relapsed/refractory chronic lymphocytic leukemia: Results of a phase III randomized double-blind placebo-controlled study9
Question Asked: What was the impact of idelalisib (Zydelig) plus bendamustine and rituximab (IBR) on progression-free survival compared with bendamustine and rituximab in relapsed/refractory chronic lymphocytic leukemia?
Abstract Conclusion: A prespecified interim analysis demonstrated that progression-free survival, the primary endpoint, and overall survival, a secondary endpoint, were superior in the investigational vs control arms. The progression-free survival was 23 vs 11 (hazard ratio = 0.33; P = 2.8 x 10-14; 95% CI: 0.24–0.45), respectively, for IBR vs BR. Patients were randomized to bendamustine and rituximab for six cycles every 28 days (bendamustine = 70 mg/m2 D1, D2 of each cycle [note a lower dose than the conventional dose of 90 mg/m2]; rituximab = 375 mg/m2 cycle 1 and 500 mg/m2 cycles 2–6) and idelalisib at 150 mg twice a day or placebo (administered continuously). Treatment with idelalisib or placebo was administered until progressive disease, death, intolerable toxicity, or withdrawal of consent. Transaminitis and diarrhea were more frequent in the IBR arm, and pneumonitis was noted only in the IBR arm (1.4%). ■
Disclosure: Dr. Abutalib reported no potential conflicts of interest.
1. Yasenchak CA, Forero-Torres A, Cline-Burkhardt VJM, et al: Brentuximab vedotin in combination with dacarbazine or bendamustine for frontline treatment of Hodgkin lymphoma in patients aged 60 years and above: Interim results of a multi-cohort phase 2 study. 2015 ASH Annual Meeting. Abstract 587.
2. Savage KJ, Connors JM, Villa DR, et al: Advanced stage classical Hodgkin lymphoma patients with a negative PET-scan following treatment with ABVD have excellent outcomes without the need for consolidative radiotherapy regardless of disease bulk at presentation. 2015 ASH Annual Meeting. Abstract 579.
3. Sawas A, Connors JM, Kuruvilla JG, et al: The combination of brentuximab vedotin and bendamustine demonstrates marked activity in heavily treated patients with relapsed or refractory Hodgkin lymphoma and anaplastic large T-cell lymphoma: Results of an international multi center phase I/II experience. 2015 ASH Annual Meeting. Abstract 586.
4. LaCasce AS, Bociek G, Sawas A, et al: Brentuximab vedotin plus bendamustine: A highly active salvage treatment regimen for patients with relapsed or refractory Hodgkin lymphoma. 2015 ASH Annual Meeting. Abstract 3982.
5. Santoro A, Mazza R, Pulsoni A, et al: Remarkable clinical efficacy, stem cell mobilization activity and good toxicity profile of the novel Begev regimen (bendamustine, gemcitabine and vinorelbine) used as salvage therapy prior to autologous stem cell transplant for relapsed/refractory Hodgkin lymphoma. 2015 ASH Annual Meeting. Abstract 581.
6. Fowler N, Nastoupil L, de Vos S, et al: Ibrutinib plus rituximab in treatment-naive patients with follicular lymphoma: Results from a multicenter, phase 2 study. 2015 ASH Annual Meeting. Abstract 470.
7. Hertzberg MS, Gandhi MK, Butcher B, et al: Early treatment intensification with R-ICE chemotherapy followed by autologous stem cell transplantation using Zevalin-BEAM for patients with poor risk diffuse large B-cell lymphoma as identified by interim PET/CT scan performed after four cycles of R-CHOP-14: A multicenter phase II study of the Australasian Leukaemia Lymphoma Study Group (ALLG). 2015 ASH Annual Meeting. Abstract 815.
8. Yasenchak CA, Halwani A, Advani R, et al: Brentuximab vedotin with RCHOP as frontline therapy in patients with high-intermediate/high-risk diffuse large B cell lymphoma: Results from an ongoing phase 2 study. 2015 ASH Annual Meeting. Abstract 814.
9. Zelenetz AD, Robak T, Coiffier B, et al: Idelalisib plus bendamustine and rituximab (BR) is superior to BR alone in patients with relapsed/refractory chronic lymphocytic leukemia: Results of a phase 3 randomized double-blind placebo-controlled study. 2015 ASH Annual Meeting. Abstract LBA-5.