Results from a recent retrospective study conducted in Germany suggest that treatment with novel agents followed by an autologous stem cell transplant may be an effective and safe salvage therapy for relapsed mul­tiple myeloma patients who previously received a transplant.

The study investigators believe that this course of treatment could po­ten­tial­ly "serve as a bridge" to a late donor transplant in certain patients.

However, the researchers point out that many of the patients included in the analysis did not receive novel agents as initial treatment. It is there­fore unclear if similar results would be observed in patients who receive novel agents as part of their initial treatment.

Background

High-dose chemotherapy followed by autologous stem cell transplantation is a common treatment option for multiple myeloma patients up to 65 years of age. In this procedure, a patient's own stem cells are collected before high-dose chemotherapy, which destroys cancerous as well as healthy cells of the bone marrow. The stem cells are later re-infused into the patient to replace the destroyed cells.

However, according to the German researchers, most patients eventually relapse after receiving a stem cell transplant and require further treatment, often referred to as salvage therapy. Novel agent regimens in­clud­ing Revlimid (lenalidomide) or Velcade (bortezomib) have been shown to be effective as salvage therapy (see related Beacon news).

Prior research has also demonstrated that a second transplant may be an effective salvage therapy for re­lapsed and refractory multiple myeloma patients who previously received a transplant (see related Beacon news).

However, the investigators state that the role of novel agents as induction therapy prior to a salvage trans­plant has not been determined yet.

Study Design

In the current study, researchers retrospectively evaluated data from 24 myeloma patients who received a transplant between 1998 and 2010 at University Hospital of the Technische Universität München in Germany as part of their salvage therapy.  All patients relapsed after prior treatment and transplantation. The patients had a median age of 64 years and had received a median of one line of therapy prior to their initial trans­plant.

Of the 24 patients included in the analysis, 29 percent initially underwent one transplant and 71 percent initially underwent two back-to-back (tandem) transplants, the second being done within 12 weeks of the first transplant.

Overall, 13 percent of patients had received initial treatment with a novel agent prior to their first transplant.  Prior to the salvage transplant which led to their inclusion in the current study, the majority of patients (96 percent) received a novel agent regimen.

For the salvage transplant, patients who were 60 years old or younger received 100 mg/m² of melphalan (Alkeran) on days 1 and 2, while patients over age 60 received 70 mg/m² of melphalan on days 1 and 2.

Patients who met particular criteria after salvage transplantation had the option of receiving a donor (allo­geneic) transplant. Overall, 38 percent of patients eventually received reduced-intensity conditioning followed by a donor transplant.

The median follow-up time from initiation of salvage therapy was 99 months.

Study Results

The median interval between first transplant and the start of salvage therapy with novel agents was 24 months. In comparison, the median time to the next treatment after salvage transplantation was 21 months.

All patients had responded to their initial transplant(s), with 21 percent reaching a complete response, 46 percent a very good partial response, and 33 percent a partial response.

Of the 23 patients evaluated after salvage transplantation, 88 percent responded, with 4 percent achieving a complete response, 38 percent a very good partial response, and 46 percent a partial response.

The median progression-free survival after initial treatment was 19 months, compared to 13 months after salvage transplantation. According to the researchers, the progression-free survival time after salvage transplantation observed in their study is noticeably higher than that of a prior study, in which the median progression-free survival after salvage transplantation was 8.5 months.

The researchers found that response to initial transplant and time to progression after initial therapy pre­dicted longer time to progression after salvage transplantation.

The median overall survival from the start of a patient's first myeloma therapy was 7.5 years.

According to the researchers, the rate of severe and life-threatening non-blood-related side effects was not significantly different between first and salvage transplants (66 percent versus 79 percent, respectively).

At the time of analysis, 54 percent of patients were alive and progression-free, including 55 percent of the patients who received a donor transplant after their salvage (own stem cell) transplant.

For more information, please see the study in Therapeutic Advances in Hematology (pdf).