CD38-Specific Monoclonal Antibody Demonstrates Encouraging Efficacy in Myeloma

Silas Inman
Published Online: June 9, 2014
Dr. Thomas G. Martin

Thomas G. Martin, MD

The CD38-specific monoclonal antibody SAR650984 demonstrated encouraging efficacy as a monotherapy and in combination with dexamethasone and lenalidomide without reaching a maximum tolerated dose in patients with heavily pretreated multiple myeloma, according to results from two early-phase clinical trials presented at the 2014 ASCO Annual Meeting.

"There's a handful of evidence to move forward with this combination. First, these drugs all have shown single-agent activity. Second, lenalidomide may increase serum IL-2 levels, and thus promote NK cell activity and enhance ADCC [antibody dependent cellular cytotoxicity]. And there's also data from xenograft models," Thomas G. Martin, MD, the associate director of the myeloma program at the University of California, San Francisco, explained during his presentation.

Single-agent SAR650984 was administered intravenously to 35 patients with relapsed/refractory multiple myeloma across a variety of doses ranging from 0.3 to 20 mg/kg, in a phase I study. Patients had a median age of 64 years and had received a median of 6 prior therapies, including immunomodulatory agents and proteasome inhibitors.

Across all doses, the overall response rate (ORR) was 24% with a stable disease (SD) rate of 41%. In patients receiving a dose ≥10mg/kg (n = 18), the ORR was 33% with a 39% SD rate.

The most common all-grade adverse events (AEs) were fatigue (48.6%), nausea (34.3%), pyrexia (28.6%), anemia (28.6%), cough (25.7%), headache (25.7%), upper respiratory infection and chills (22.9%), dyspnea (20%), constipation (17.1%), and diarrhea and vomiting (14.3%). The most common, greater than grade 3 AE was pneumonia (9%).

In a separate phase Ib study, 13 patients with relapsed/refractory multiple myeloma were treated with SAR650984 at either 3, 5, or 10 mg/kg every 2 weeks. Lenalidomide was administered at 25 mg on days 1 through 21, and dexamethasone was administered at 40 mg once per week in a 28-day cycle.

The ORR across all doses was 58%, which was comprised of 1 partial response (PR) at the 3-mg/kg dose, 1 PR and 1 very good PR (VGPR) in the 5-mg/kg arm, and 1 PR and 3 VGPRs in the 10-mg/kg cohort.

Based on these findings, an expansion cohort was opened that enrolled an additional 18 patients who received treatment with the 10-mg/kg dose of SAR650984. Altogether, in patients treated with the 10-mg/kg dose (n = 24), the ORR was 63% (25% VGPR, 38% PR). When considering minimal responses, the clinical benefit rate was 67%.

In an analysis of response rates based on prior therapy, it was found that patients refractory to lenalidomide (n = 25) had an ORR of 48% (20% VGPR, 28% PR). Those refractory to bortezomib (n = 16) had an ORR of 44% (25% VGPR, 19% PR) and those refractory to pomalidomide (n = 9) had an ORR of 33% (11% VGPR, 22% PR). Strikingly, in 6 patients that were nonrefractory to lenalidomide, the ORR was 100% (33% VGPR, 67% PR).

The most frequent AEs included nausea (19%), cough (19%), fatigue, muscle spasm, and infection (n = 16% each). Greater than grade 3 neutropenia occurred in 13% of patients and thrombocytopenia was apparent in 10%. One patient discontinued therapy after the first treatment due to a grade 3 infusion reaction. 

Related Articles
Of the many signaling cascades being targeted for therapeutic intervention in cancer, one of the most important and best understood is the MAPK pathway, particularly the RAS/RAF/MEK/ERK cascade.
Several advances in the treatment of metastatic melanoma have occurred in the last 5 years, one of which has been the approval by the FDA of targeted treatments for patients with melanomas harboring a BRAF mutation.
Unlike many other types of tumors, melanoma can be detected early in its progression by visual, noninvasive methods.
Only in the last 2 decades or so have sufficient data become available to statistically associate high mitotic rate with survival in melanomas.
JTT Articles
Q & A With Dr. Sunil Verma: Targeted Treatments for HER2-Positive Breast Cancer
Immunotherapies in CRPC: Progress Evident but Not Without Challenges
The Transformation of Treatment in CLL: A Q & A With Dr. William G. Wierda
External Resources

AJMC
HCPLive
OncLive
PainLive
Pharmacy Times
Physicians' Education Resource
Physician's Money Digest
Internal Resources

Articles
Fellows
Publications
Targeted Communications
Resources
Connect With Us:

About Us
Advertise
Contact Us
Privacy Policy
Terms & Conditions
Intellisphere, LLC
666 Plainsboro Road
Building 300
Plainsboro, NJ 08536
P: 609-716-7777
F: 609-716-4747

Copyright TargetedOnc 2013
Intellisphere, LLC. All Rights Reserved.