Adding Vorinostat to Revlimid Post-transplant Maintenance Therapy May Benefit Myeloma Patients, Phase 1 Trial Shows

Adding the lymphoma therapy vorinostat to Revlimid (lenalidomide) maintenance therapy may deepen responses to stem cell transplants and prolong survival outcomes in multiple myeloma patients, long-term results of a Phase 1 clinical trial show.

Results were published in the journal Biology of Blood and Marrow Transplantation in the study, “Lenalidomide and Vorinostat Maintenance after Autologous Transplantation in Multiple Myeloma: Long- Term Follow-Up.”

Autologous stem cell transplant (ASCT) is often the first line of therapy for treating multiple myeloma, and while this procedure has proven benefits, it isn’t typically curative. Thus, it is commonplace for those who undergo ASCT to then be placed on a regimen of cancer-killing agents, which is called maintenance therapy.

While standard post-transplant maintenance therapy for myeloma is Celgene‘s Revlimid, it has been proposed that adding additional agents to Revlimid could be beneficial; however, safety concerns have proven an obstacle.

Vorinostat (marketed as Zolinza by Merck for skin lymphoma) is a compound that can stop cancer cells from dividing and kill them, and it may work well with other cancer therapies.

In the open-label Phase 1 trial (NCT00729118), researchers at the The Ohio State University Comprehensive Cancer Center addressed whether a combination of vorinostat plus Revlimid could extend clinical responses achieved after transplant and prolong the lives of multiple myeloma patients.

Sponsored by Merck, the study included 16 patients (median age 58 years) undergoing their first stem cell transplant. About three months after the transplant, they received oral, once-daily vorinostat for one-week-on, one-week-off in 28-day cycles, along with oral Revlimid in the first three weeks of each cycle.

The trial’s main goal was to determine the safety of the combination; efficacy results, such as duration of response, time to disease progression or death, time to response, and overall survival were assessed as secondary measures.

Safety results have been previously published, showing that this combination has an acceptable safety profile with no added toxicity compared with Revlimid maintenance therapy.

Long-term results of this trial, assessed after a median follow-up of 89.8 months, showed that the combination deepened responses to the stem cell transplant and extended the time to disease progression or death compared with other studies of Revlimid maintenance therapy.

Before starting maintenance therapy, two patients had a stringent complete response (sCR), two had a complete response (CR), two had partial responses (PR), and another 10 had very good partial responses (VGPR). Stringent complete responses and very good partial responses are deeper complete and partial responses, respectively.

Among the 12 patients who were not in complete response prior to maintenance therapy, half experienced further disease reductions after the treatment, including one PR that turned into a VGPR, one VGPR that turned into an sCR, and four VGFRs that became CRs.

In addition, these patients lived without signs of disease worsening for a median of 64.3 months after the transplant, which compares favorably with the 52.8 months seen with maintenance therapies using Revlimid alone. Six years after their transplant, 69% of patients were still alive.

The researchers noted no new toxicities or safety concerns over the long-term follow-up. Common side effects included decreased white blood cell counts, anemia, nausea, diarrhea, and fatigue.

They concluded that, “the use of lenalidomide plus vorinostat could prove to be a promising maintenance strategy in patients with newly diagnosed multiple myeloma,” also noting that “a phase III randomized study of lenalidomide vs. combination with vorinostat is warranted.”