Advances in the development of multiple myeloma drugs have had a profound impact on the way the disease is treated. Given the efficacy and relative safety of these novel agents, studies are being conducted to determine whether they may be as effective, or possibly even more effective, than an autologous stem cell transplant ^[1](ASCT). Two such studies were presented June 6 at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

Results from the two studies suggest that ASCT (in which a patient’s own stem cells are transplanted after chemotherapy) may not be necessary if replaced with novel agents. However, Dr. Jean-Luc Harousseau of the Rene Gauducheau Cancer Center in France cautioned that further studies are still required.

“Is it really time to abandon autologous transplantation upfront?” Dr. Harousseau asked in a discussion session that followed the two presentations. “My answer is maybe, but not yet.”

Results of the first study are discussed in this article. Results of the second study will be discussed in Part 2 ^[2].

Conventional Chemotherapy Plus Revlimid May Be As Effective As ASCT In Newly Diagnosed Myeloma Patients

Dr. Antonio Palumbo of Torino University, Italy presented interim results of an ongoing Phase 3 trial. Newly diagnosed patients received initial treatment (induction) with Revlimid ^[3] (lenalidomide) and low-dose dexamethasone ^[4] (Decadron), abbreviated Rd. Half of the patients then received conventional chemotherapy plus Revlimid – melphalan ^[5] (Alkeran), prednisone ^[6], plus Revlimid (MPR). The other half received high-dose melphalan and ASCT (MEL200).

In a phase of the trial that is still ongoing, half of the patients who received MPR and half of the patients who received MEL200 will also receive long-term, low-dose Revlimid treatment (known as maintenance therapy), while the other half will not receive maintenance.

To date, the study has found that both MPR and MEL200 similarly improved the response to Rd induction. Progression-free survival and overall survival are similar for both groups. Treatment with MPR, however, resulted in far fewer side effects than MEL200 therapy.

Efficacy And Safety Of Rd Induction

A total of 402 newly diagnosed patients were enrolled in the Phase 3 trial. All patients received 25 mg Revlimid on days 1 to 21 of a 28-day cycle and 40 mg dexamethasone on days 1, 8, 15, and 22. To increase the number of stem cells for transplantation, patients also received cyclophosphamide ^[7] (Cytoxan) and granulocyte colony-stimulating factor during this time.

After four 28-day cycles of Rd induction, complete response was achieved in 6 percent of patients, very good partial response in 31 percent, and partial response in 49 percent.

Furthermore, 91 percent of patients were able to collect the minimum number of stem cells required for transplantation. This confirmed that Rd induction does not interfere with adequate stem cell collection for transplant.

The Rd induction regimen was very well tolerated, with severe side effects experienced in less than 10 percent of participants.

“This is a very good safety profile,” said Dr. Palumbo of the Rd induction regimen. “The complete remission rate is not so high, but the safety profile is certainly one of the best you can find in combination, including novel agents.”

Efficacy And Safety Of MPR Versus MEL200 Therapy

After Rd induction, about half of the enrolled patients were treated with MPR while the remaining patients received MEL200 therapy. At least three cycles of MPR or one course of MEL200 improved the initial complete response rates in these groups to 13 percent and 16 percent, respectively.

Progression-free survival 12 months following MPR or MEL200 treatment was the same for both groups (91 percent). Likewise, overall survival was similar for both groups (97 percent vs. 98 percent).

“Despite the short follow up, certainly the combination including a new agent is reducing the difference between standard treatment and ASCT,” said Dr. Palumbo in reference to the survival data.

“The interesting thing is that the early results are remarkably similar,” said Dr. Brian Durie of Cedars Sinai in Los Angeles and the International Myeloma Foundation.

MPR therapy was much better tolerated by patients than MEL200. In young patients, the rate of significantly low white blood cell counts was much lower for MPR patients than MEL200 patients (15 percent vs. 86 percent). Similarly, significantly low platelet levels were a side effect for most MEL200 patients (87 percent), while only 8 percent of MPR-treated patients had the same side effect.

Dr. Antonio Palumbo stated, “The comparison is easy in terms of safety profile. No question there is a major advantage for conventional treatment [MPR].”

For more information, please see abstract 8015 ^[8] at the ASCO meeting ^[9] website.