Highlights from Lymphoma and Myeloma 2014: An International Congress on Hematologic Malignancies
Christan M. Thomas, PharmD
Clinical Assistant Professor
St. John’s University College of Pharmacy
Clinical Pharmacist, Lymphoma/Myeloma
NewYork-Presbyterian, Weill Cornell Medical Center
New York, NY
New targets and debates on appropriate therapies came to the forefront during Lymphoma and Myeloma 2014: An International Congress on Hematologic Malignancies, which took place in New York, NY, October 23–25, 2014.
Since its inception in 2000, the conference has become one of the largest international meetings on hematologic disorders. During the course of 3 days, an interdisciplinary group of clinicians discussed basic science, new therapies, and existing data on the treatment of multiple myeloma, chronic lymphocytic leukemia (CLL), and lymphomas. The following are summaries of selected congress presentations.
Novel Agents: What Will Be Available in the Next Few Years?
Kenneth Anderson, MD, concluded that with the advent of new therapies and specific targeting of the tumor microenvironment, multiple myeloma would become a chronic illness with sustained complete responses in a significant number of patients. Anderson highlighted several new agents under investigation, including monoclonal antibodies, antibody-drug conjugates, and vaccines against multiple myeloma–specific peptides.
Elotuzumab, a monoclonal antibody directed against signaling lymphocyte activation molecule (SLAMF7 or CS1), has been well tolerated in patients during phase 1 and 2 trials. Infusion reactions have been mitigated using premedications. Early trials show overall response rates ranging from approximately 27% as a monotherapy to 84% when given in combination with lenalidomide and dexamethasone. Ongoing phase 3 trials will examine this combination for both initial therapy and in relapsed or refractory disease.
Another monoclonal antibody in development, daratumumab, targets CD38. Early, small studies show marked decreases in M-protein and positive results in overall response rates in the majority of patients. Phase 3 studies will examine daratumumab both as a monotherapy and in combination with lenalidomide/dexamethasone. Another anti-CD38 monoclonal antibody—SAR650984—also is in development.
Induction Therapies in Transplant-Eligible Patients with Multiple Myeloma
Tomer Mark, MD, discussed how to approach treatment in transplant-eligible patients with multiple myeloma in the era of novel therapies. Based on available data, Mark said combinations of novel agents lead to deeper responses pretransplant, which tend to translate into better responses posttransplant.
As a result of trials with combinations such as CyBorD (cyclophos- phamide, bortezomib, dexamethasone), BiRD (clarithromycin, lenalidomide), and VRD (bortezomib, lenalidomide, dexamethasone), Mark suggested that any three-drug combination may be an appropriate choice for initial therapy. According to Mark, the similar response over time with the various first-line treatment strategies indicate that many good induction therapies exist and that the choice should be tailored to the patient.
In addition, Mark noted that carfilzomib may enhance initial response rates and decrease minimal residual disease (MRD). Mark cited two studies in which the majority of patients were MRD negative with the addition of carfilzomib. Progression-free survival in these patients was between 89% and 91% at 3 years and 18 months, respectively. At this point, however, Mark cautioned that little is known regarding how stem cell transplant may negate initial differences in response, consequences of long-term use, or implications for subsequent therapies.
Ibrutinib: Analysis of Its Pivotal Data
Richard Furman, MD, one of the primary authors on many initial ibrutinib trials and the CLL cochair for the congress, reviewed current data on the Bruton’s tyrosine kinase (BTK) inhibitor and offered insights from his vast experience with the drug.
Furman noted that as more and more data are published, both response rate results and adverse effect profiles will continue to evolve. One take-home point from this session was that achieving best response was time dependent, and the proportion of patients with either complete or partial responses tended to increase during follow-up. The proportion of patients with a partial response with lymphocytosis also decreased as data matured.
In terms of side effects, atrial fibrillation became one notable effect during the RESONATE trial. In this trial, overall rates of atrial fibrillation were 5% with 3% reported at grade 3 or above. Furman said that additional data are needed to fully elucidate true clinical relevance— especially for the grade 3 or above reactions.
Also of concern with the administration of ibrutinib is the possible increased bleed risk. In the RESONATE trial, 44% of patients in the ibrutinib arm experienced bleeding. Grade 3 or 4 bleeds, however, occurred in only 1% of patients who experienced bleeding. The direct effect of BTK on platelets, as well as other off-target effects currently being explored, could modulate this bleed risk, Furman said.
Another particularly troublesome side effect of ibrutinib is the relatively high rate of diarrhea experienced by patients. Furman noted that this effect is reversible and generally only symptomatic when food is present in the stomach. He suggested patients take ibrutinib at night and avoid eating after ingesting the drug. A dose reduction also may be necessary, if diarrhea continues.
Idelalisib: Analysis of Its Pivotal Data
Jeff Sharman, MD, summarized available data on idelalisib, which recently received U.S. Food and Drug Administration approval, and also offered suggestions on when to use the medication in therapy.
In the United States, idelalisib is indicated for relapsed CLL in combination with rituximab in patients for whom rituximab alone would be appropriate therapy due to other comorbidities. In addition, idelalisib may be used as monotherapy in relapsed follicular lymphoma or re- lapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies. European indications also include idelalisib as first-line therapy for CLL patients with a 17p deletion or TP53 mutation and who are not suited for chemoimmunotherapy.
The drug also carries four black box warnings: fatal and/or serious hepatotoxicity, fatal and/or serious and severe diarrhea, fatal and serious pneumonitis, and fatal and serious intestinal perforation. Deaths from each of these adverse effects occurred in studies at a rate of less than 1%.
Based on indications, available data, and side effect profile, Sharman proposed several situations in which idelalisib might be a good therapeutic choice versus ibrutinib. He suggested idelalisib for CLL patients receiving rituximab and those on blood thinners with a history of atrial fibrillation, with pre-existing renal insufficiency, and possibly a 17p deletion. In contrast, Sharman recommended using ibrutinib in patients with abnormal liver function, history of bowel difficulties, lung issues, or when monotherapy is preferred.
Although not a comprehensive review, presentations from the congress are available for free download. For additional information and to download slides, visit www.imedex.com/ lymphoma-myeloma-conference. Slides may be found by clicking on the archives link from the home page.
Next year’s congress is scheduled for October 22–24, 2015, at the Waldorf Astoria Hotel in New York, NY.