WHAT'S HOT AT ASH

Presentations likley to have an impact on patient care were highlighted in a press webinar held ahead of the American Society of Hematology (ASH) annual meeting. Held this year in San Diego, California, the meeting starts on Friday, December 2.

Practice-changing results that will affect the treatment of some patients with lymphoma come from three phase 3 trials, commented Stephanie Lee, MD, MPH, secretary of ASH and a professor of medicine at the University of Washington in Seattle.

The GALLIUM study shows the new anti-CD20 antibody obinutuzumab (Gazyva, Genentech) to be superior to the older agent rituximab (Rituxan, Genentech) when used for induction and maintenance in adult patients with previously untreated follicular lymphoma (abstract 6). The new drug, approved for follicular lymphoma earlier this year, showed a clinically meaningful improvement in progression-free survival (PFS; 34% reduction compared with rituximab-based therapy).

The authors, headed by Robert Marcus, MD from King's College Hospital in London, United Kingdom, say that the results support obinutuzumab with chemotherapy becoming a new standard of care in previously untreated patients with folicular lymphoma.

However, there was no difference in overall survival and side effects increased with obintuzumab when compared with rituximab.

"This trial is important because it shows us that obinutuzumab is more effective than rituzumab at prolonging time to relapse, but there are some caveats as it does look like it has higher toxicity," Dr Lee commented.

The ALCANZA study shows that brentuximab ventolin (Adcetris, Seattle Genetics) has significantly superior clinical outcomes when compared with physician's choice of therapy (methotrexate or bexarotene) in the rare disorder of CD30-expressing cutaneous T cell lymphoma (abstract 182).

The authors, headed by Youn Kim, MD, from Stanford University School of Medicine, California, report that the clinical outcomes with brentuximab ventolin were "far superior," with highly statistically significant improvements in both overall response rates and median PFS (13.2 months vs 3 months with physician's choice of therapy).

"This trial shows that brentuximab ventolin has significant advantages over two commonly used treatments for this disease," Dr Lee commented. She noted that it is difficult to conduct randomized trials in rare diseases, but these investigators were able to do so and come to a fairly definitive conclusion.

he LyMa trial in younger patients with mantle cell lymphoma (MCL) shows that rituximab maintenance after autologous stem cell transplantation prolongs survival (abstract 145).

This study, conducted in patients who were responding well after transplanation, showed that 4-year PFS and overall survival were better in patients randomly assigned to rituximab than in those receiving placebo.

The study authors, led by Steven Le Gouill, MD, PhD, from Nantes University Hospital in France, conclude that rituximab maintenace (one infusion every 2 months for 3 years) is a new standard of care for young patients with MCL.

"This trial provides good evidence that rituximab maintence improves patient outcomes after transplant," Dr Lee said. Some clinicians have already been doing this, she commented, but for those who have not, this study provides good data showing a survival advantage.

Practice-Changing Results in CLL

Dr Lee also highlighted one abstract that could change practice in the treatment of some patients with leukemia.

Final results from the German CLL M1 study (abstract 229) show that maintenance therapy with lenalidomide (Revlimid, Celgene) after front-line chemoimmunotherapy substantially prolongs PFS in patients with high-risk chronic lymphocytic leukemia (CLL).

These patients with CLL underwent four cycles of frontline chemoimmunotherapy and had at least a partial response; they were judged to be high risk because of their cytogenetic profile or because of the amount of residual disease, Dr Lee explained. They were randomly assigned 2:1 to lenalidomide or placebo, and only 89 patients were analyzed. The aim had been 200 patients, but the study was stopped early because of the positive results at interim analysis, she said. After a median observation time of 17.7 months, the hazard ratio for PFS was a very impressive 0.198, she commented. The median PFS in the placebo group was 14.6 months and was not reached in the lenalidomide group.

The results suggests that maintenance with lenalinomide is benefiial in these patients with high-risk CLL who have residual disease after initial chemoimmunotherapy, Dr Lee commented.

New Results With CAR T Cell Therapy

Charles Abrahms, MD, ASH president and professor of medicine at the University of Pennsylvania and Children's Hospital of Philadelphia, highlighted new research results with chimeric antigen receptor (CAR) T cell therapy.

This novel treatment approach involves taking T cells from a patient, genetically engineering them to attack antigens present on tumor cells, and then infusing them back into the body. It has shown some spectacular results in eliminating leukemia and lymphoma, but it has also led to severe adverse reactions.

"Cytokine release syndrome and neurological symptoms do occur with this therapy, so it's not for the fainthearted, but we can usually carry patients through," Dr Abrahms commented. Usually this therapy is given within a university setting, with specially trained personel who have experience with the technology and its adverse effects.

But a new study shows that the CAR T cell technology can be brought out into the broader setting of the community, Dr Abrahms commented.

The multicenter pivotal phase 2 ZUMA-1 trial with the Kite anti-CD19 CAR T cell product (abstract LBA-6) involved 111 patients from 22 instititions. The CAR T cells were engineered within 17 days.

The trial shows that this CAR therapy induces complete remissions in patients with refractory diffuse large B cell lymphoma, Dr Abrahms commented. The results were rather impressive, he commented, with an overall response rate of 76% and a PFS estimate at 3 months of 56%.

Of note, however, was that this trial was conducted across many different clinical sites, some of which had no experience using CAR T cell therapy.

The other abstract that Dr Abrahms highlighted was research on a new target for CAR T cell therapy. To date, much of the success with this investigational approach has been achieved with anti-CD19 CAR T cell therapy for relapsed/refractory acute lymphoblastic leukemia (ALL). However, not all patients respond, and CD19-negative escape has been observed. To overcome this problem and to test an alternative target, researchers at the National Cancer Institute, headed by Nirali N. Shah, MD, developed an anti-CD22 CAR T cell. At the meeting, they will report results from the first few patients treated with this product (abstract 650), all of whom had CD22+ ALL and had already undergone at least one allogeneic hematopoietic stem cell transplant (HSCT)