Top Takeaways from ASCO: Leukemia and Lymphoma

Monoclonal antibodies demonstrate safety, effectiveness in 3 trials.

CHICAGO — The positive outcomes for several novel treatments that may soon be included in the therapeutic armamentarium for leukemia and lymphoma stand to make treatment options for these cancers more robust and efficacious, according to findings presented at the 2015 ASCO Annual Meeting. Here, physicians shared their Top Takeaways for the treatment of leukemia and lymphoma with Healio.com.

Ibrutinib ‘fairly impressive’ in treatment of leukemia, lymphoma subtypes

A randomized, double-blind, placebo-controlled, phase 3 study of ibrutinib combined with bendamustine and rituximab vs. bendamustine and rituximab plus placebo demonstrated “fairly impressive results,” said Jonathan Gerber, MD, director of the leukemia program at the Levine Cancer Institute in Charlotte and a HemOnc Today Editorial Board member.

Jonathan Gerber

The ibrutinib trial was conducted in 578 patients with previously treated chronic lymphocytic leukemia and small lymphocytic lymphoma, with 289 patients each randomized to both the ibrutinib and placebo arms. At a median follow-up of 17.2 months, PFS was significantly longer for patients in the ibrutinib arm compared with the placebo arm (median not reached vs. 13.3 months; HR = 0.203; 95% CI, 0.150-0.276). Overall response rate was 82.7% vs. 67.8% (P < 0.0001). Rates of most adverse events was similar between arms.

“It looked like, across the board, that ibrutinib increased responses [and] seemed to be fairly well tolerated,” Gerber said. “I think one of the questions that was interestingly raised is how much the bendamustine and rituximab may add to ibrutinib alone, which has had some impressive results. This trial was designed to look at just the combination of ibrutinib with bendamustine and rituximab against bendamustine and rituximab alone. It will be interesting to potentially begin to re-think the paradigm. I think that the results are enough to begin to move forward and begin thinking about this as a more standard regimen.”

PERSIST trial

Gerber also discussed the PERSIST-1 phase 3 study, in which patients with myelofibrosis were treated with pacritinib, a JAK2 inhibitor.

“Rather than being a JAK1 and JAK2 inhibitor, [pacritinib] is really more selective for JAK2,” he said, adding that the agent also targets the FLT3 receptor.

Spleen volume reduction at 24 weeks was 19.1% for patients treated with pacritinib vs. 4.7% for patients receiving the best available therapy (P = 0.0003) in the intent-to-treat group and 25% vs. 5.9% (P = 0.0001) in the evaluable population. Nearly 80% of patients in the best available therapy arm (79%) crossed over to treatment with pacritinib; 21% had achieved a greater than 35% reduction in spleen volume at data cutoff. Total symptom score composite V1 + V2 response rates were 24.5% for pacritinib vs. 6.5% for best available therapy by intent-to-treat and 40.9% vs. 9.9% in evaluable patients (both P < 0.0001).

“[Pacritinib] actually also had some impressive responses,” Gerber told Healio.com. “It was fairly well tolerated – diarrhea and some other gastrointestinal side effects seemed to be the most significant, but few patients had to stop because of that. They had some impressive results in reducing splenomegaly and related symptoms and seemed to be able to do it without much impact on counts. Really, that’s been a limiting factor for the existing JAK2 inhibitor ruxolitinib, so it was interesting to hear that perhaps now we have an agent that may be able to treat splenomegaly but not have cytopenias as a significant side effect.”

Results from the GADOLIN study

This phase 3 trial in patients with rituximab-refractory, indolent non-Hodgkin’s lymphoma demonstrates obinutuzumab, an anti-CD20 monoclonal antibody, in combination with bendamustine is safe and effective compared to treatment with bendamustine alone, according to Joshua Brody, MD, professor of medicine, hematology and oncology and director of the Lymphoma Immunotherapy Program, Icahn School of Medicine, Mount Sinai Hospital, New York.

Joshua Brody

Patients (n = 396) were randomized to either bendamustine alone (n = 202; 198 treated) or obinutuzumab and bendamustine (n = 194). Median observation time was 20 months for the bendamustine group and 22 months for patients treated with obinutuzumab and bendamustine. All patients receiving obinutuzumab and bendamustine who did not have progressive disease then received obinutuzumab monotherapy every 2 months for up to 2 years.

“The goal was to prolong the PFS of these patients,” Brody said. “The results were actually remarkable. Patients with bendamustine alone had median PFS of about 14 months, whereas patients with the combination therapy with obinutuzumab had a PFS of more than twice that, approximately 29 months."

The addition of antibody therapy to the chemotherapy agent bendamustine, particularly in patients who experience little benefit from rituximab, an earlier anti-CD20 antibody, “is of profound significance,” Brody told Healio.com. “We need to be able to improve upon the chemotherapy results. Monoclonal antibody therapy is both a safe and - now we can clearly see - highly effective way to accomplish that.” – by Julia Ernst, MS

References:

Chanan-Khan AA, et al. Abstract LBA7005.

Mesa RA, et al. Abstract LBA7006.

Sehn LH, et al. Abstract LBA8502.

All presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosures: Brody and Gerber report no relevant financial disclosures.