Photo by Linda Bartlett
NEW ORLEANS—A small study suggests that treatment with lenalidomide and dexamethasone (len-dex) prompts an increase in cancer stem cells (CSCs) for patients with newly diagnosed multiple myeloma (MM).
However, adding an anti-CD19 monoclonal antibody (mAb) to the regimen can reduce CSCs.
Most patients who received the mAb, MEDI-551, experienced a decrease in CSCs, but the cells rebounded after the patients stopped receiving MEDI-551.
And those patients who did not see a decrease in CSCs progressed. However, some patients are still in response and remain on treatment with len-dex.
The investigators believe these early results suggest prolonged treatment with len-dex and MED-551 may be safe and clinically beneficial for MM patients.
The results were presented at the 2016 AACR Annual Meeting (abstract CT102).
The study included 17 patients with newly diagnosed MM. They had a median age of 65 (range, 34-73). Most had ISS stage I (n=11), 2 had stage II, and 4 had stage III. Seven patients had t(4;14).
“We chose to carry out this clinical trial in newly diagnosed patients because our original data showed that CD19 was almost always expressed by myeloma stem cells in these patients, whereas we don’t know if that is the case in more advanced patients,” said investigator William Matsui, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.
The patients received 28-day cycles of len-dex (len at 25 mg PO, days 1-21, and dex at 40 mg PO, weekly). Patients received MEDI-551 (at 4 mg/kg IV) in cycle 3 (day 1, 8) and cycle 4 (day 1). Responding patients continued on len-dex.
The investigators measured MM CSCs by quantifying the growth of MM colonies (CFU-MM) from marrow aspirates at baseline and at the end of cycles 2 and 4.
The team quantified peripheral blood CSCs by flow cytometry (CD19+CD27+ALDH+) at baseline and the end of cycles 2, 4, 5, and 7.
“We wanted to see if these 2 assays gave similar results, and, in this clinical trial, they were almost identical,” said investigator Carol Ann Huff, MD, also of Johns Hopkins.
“Since it is much easier to draw blood than bone marrow from our patients, we think that we can primarily use blood to track multiple myeloma stem cells in the future.”
Response
Two patients did not receive MEDI-551 due to progressive disease and noncompliance. So the investigators assessed responses in 15 patients.
After cycle 2 (len-dex alone), there were 3 very good partial responses (VGPRs), 10 partial responses (PRs), 1 molecular response, and 1 case of stable disease.
After cycle 4 (len-dex plus MEDI-551), there were 6 VGPRs, 8 PRs, and 1 molecular response.
Ten patients who completed treatment with MED-551 remain on len-dex. At the end of cycle 7, there was 1 complete response, 8 VGPRs, and 1 PR.
CFU-MM
When compared to baseline, bone-marrow-derived CFU-MM increased a median of 2.5-fold (range, 0.4-7.4) after cycle 2 but decreased a median of 0.48-fold (range, 0.14-0.85) in 14 patients after cycle 4.
The investigators compared these results to 5 newly diagnosed MM patients who only received standard treatment with len-dex.
In these patients, CFU-MM increased a median of 9.3-fold (range, 4-14) at a median of 4 months (range, 2-4). This is in spite of the fact that all of these patients had a PR or better.
Circulating CSCs
Compared to baseline, circulating MM CSCs increased a median of 1.6-fold (range, 0.4-8.6) in 14 patients after cycle 2 but decreased a median of 0.6-fold (range, 0.01-7.4) in 13 patients after cycle 4.
At the end of cycle 5, MM CSCs had increased in 4 of the 10 patients who were still on len-dex. By the end of cycle 7, MM CSCs had increased in 8 of the patients.
Circulating MM CSCs increased by the end of cycle 4 in 2 patients, and both had progressed by end of cycle 7.
Safety and next steps
The investigators said there were no serious adverse events in this trial, but 2 patients experienced grade 2 infusion reactions after the first MEDI-551 dose.
The team plans to conduct further studies to assess the long-term impact of MED-551 in MM patients and determine how the mAb might work in combination with other treatments, particularly transplant.
“In other studies at Johns Hopkins, we have found that antibody therapies can work much better after a bone marrow transplant, especially allogeneic transplants,” Dr Matsui said.
Funding and drugs for this study were provided by MedImmune Inc., the developers of MEDI-551. Drs Huff and Matsui served as a paid scientific advisory board member and a consultant to MedImmune Inc., respectively.
