ASCO 2013: Single-agent Lenalidomide Produces Promising Results in Relapsed/Refractory Mantle Cell Lymphoma

jruanBy Jia Ruan, MD, PhD

Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma (NHL) characterized by a short remission duration to standard therapies, poor prognosis, and median overall survival of 4-5 years. The immunomodulatory agent lenalidomide has consistently exhibited a tolerable level of safety in multiple phase II studies of relapsed/refractory aggressive NHL and MCL post-bortezomib.  At the recent 2013 annual meeting of the American Society of Clinical Oncology, Dr. Thomas E. Witzig of the Mayo Clinic presented results from a combined analysis of multiple phase II trials testing the efficacy and safety of single-agent lenalidomide in relapsed/refractory MCL patients.

Of the 206 patients with relapsed/refractory MCL the overall response rate with lenalidomide was 32%, with a median time to response of 2.1 months and median duration of response of 16.6 months. Kaplan-Meier estimates for median progression free survival and overall survival were 5.4 and 23.9 months, respectively. Mean daily dose of lenalidomide was 21 mg.  Grade 3/4 adverse events included neutropenia (44%), thrombocytopenia (29%), anemia (11%), and fatigue (7%), other side effects included tumor flare reaction (7%), venous thromboembolic events (7%), and invasive second primary malignancies (3%).

This study adds to the growing body of literature supporting the promise of lenalidomide for treating patients with MCL.  At the Weill Cornell Lymphoma Program these breakthroughs are augmented by our own trials exploring the utility of lenalidomide in treating patients with MCL.

Update: this study is closed to enrollment. 

The Weill Cornell Lymphoma Program is now enrolling patients in a new, investigator-initiated phase II study of lenalidomide in combination with rituximab in patients with previously untreated MCL (NCT01472562). The purpose of the study is to test the synergy of combining lenalidomide, a biological agent that targets the tumor micro-environment, with rituximab, an antibody that targets lymphoma cells. By including a maintenance phase of lenalidomide and rituximab therapy, we hope to improve treatment effectiveness and maintain quality of life for patients.

This is an outpatient treatment strategy because lenalidomide, the study medication, can be taken at home.  After the first month on study, patients will be seen in clinic on average once a month.  The study has two phases:

Induction Phase, Weeks 1-48:

  •  Treatment dose lenalidomide taken by mouth on days 1-21 of a 28-day cycle for 12 cycles
  •  Rituximab infusion for a total of 9 doses

Maintenance Phase, Week 49 until disease progression or for a maximum of 5 years from study entry:

  • Maintenance dose lenalidominde taken by mouth on days 1-21 of a 28-day cycle
  • Rituximab infusion one dose every 8 weeks

ASCO 2013: Impact of Interval Between Diagnoses and Initiation of Curative Chemotherapy on Survival of Patients with Diffuse Large B-cell Lymphoma

peter martin photoBy Peter Martin, MD

A common question arising among patients with newly diagnosed DLBCL is how soon to begin treatment. While it is generally considered more appropriate to start chemotherapy sooner rather than later after diagnosis, the exact impact of this time interval on treatment outcomes is unknown. At the recent Annual Meeting of the American Society of Clinical Oncology in Chicago, Dr. Kevin A. Hay from the University of British Columbia presented the results of a retrospective study evaluating the association of patient outcomes with time to initiation of treatment.

Dr. Hay retrospectively divided 793 patients with DLBCL and at least one cycle of R-CHOP into four groups based on the amount of time between initial diagnosis and beginning of therapy. A total of 25% of respondents received R-CHOP within 2 weeks of diagnosis, 31% in 2-4 weeks, 37% in 5-8 weeks, and 7% at longer than 8 weeks. Interestingly, there was no statistically significant difference in survival between the groups. The authors concluded that the timing of chemotherapy initiation appeared to be related to clinical factors (i.e., sicker patients were treated sooner) rather than medical system or socioeconomic barriers. While detrimental outcomes were lacking in those patients who began treatment after 8 weeks, they recommended beginning chemotherapy as soon as possible after an initial diagnosis of DLBCL.

ASCO 2013: Post-therapy Surveillance Imaging has Limited Use in Detection of Relapse of Non-Hodgkin Lymphoma

peter martin photo

By Peter Martin, MD

Despite the frequent use of routine post-therapy imaging as a means of early detection of lymphoma relapse, there is limited evidence that regular scanning improves patient outcomes. Two groups reported on their experience with surveillance imaging at the recent annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Quoc Van Truong of the West Virginia School of Medicine retrospectively evaluated 77 patients with non-Hodgkin lymphoma that had relapsed after achieving a complete response with initial treatment. Despite the frequent use of routine imaging, nearly 80% of relapses were detected by patient-reported symptoms and not surveillance imaging. Overall, there was no survival difference between the groups of patients whose relapse had been detected by scans versus those reporting additional symptoms. Additionally, surveillance imaging led to 2 false positive scans resulting in unnecessary invasive procedures.

Dr. Carrie A. Thomas of the Mayo Clinic reported on an analysis of 644 patients with DLBCL seen at the Mayo Clinic or University of Iowa between 2002 and 2009. A total of 537 patients entered post-treatment observation, and 109 of these patients relapsed while 41 died from other causes. At the time of relapse, 68% were symptomatic, 42% had an abnormal physical exam, 55% elevated LDH, and 87% had more than one of these features. Of the 38 patients whose relapse was detected during a planned visit, 26 displayed clinical features of relapse, while the relapse of the other 12 patients was detected by planned surveillance scan. Of these 12 relapses exclusively detected by the planned surveillance scan; 4 presented a low-grade or other subtype and 8 had DLBCL (4 of whom had equivocal/positive scans at the end of treatment). The authors concluded that post-therapy surveillance scans have little value in detecting DLBCL relapse.

These studies add to the growing body of literature suggesting that lymphoma patients that achieve a complete remission from first-line therapy may not benefit from routine imaging. We recommend that patients discuss plans for post-treatment surveillance with their physician.