The 56th American Society of Hematology Meeting (ASH) took place in early December 2014, in San Francisco, California, USA. This meeting is an annual highlight in the field of haematology where updated results from the latest trials in haematological diseases are presented for discussion. As has been the case in recent years, many trials were focused on myeloma and there were several notable presentations which can give myeloma patients much hope for future treatment. Below is summary of some the most important myeloma studies presented at the ASH 2014 meeting.
1. Abstract 79: Carfilzomib, Lenalidomide, and Dexamethasone vs Lenalidomide and Dexamethasone in Patients (Pts) with Relapsed Multiple Myeloma: Interim Results from ASPIRE, a Randomized, Open-Label, Multicenter Phase 3 Study (K Stewart et al)
This study was for patients with relapsed myeloma (i.e. myeloma that has already been treated and has returned). The study included 792 patients that were divided into 2 groups. The first group received a standard treatment for relapsed myeloma – lenalidomide (revlimid) and dexamethasone (Rd) whilst the second group also received Rd in addition to a new treatment called carfilzomib (trade name krypolis) – regimen called KRd. Like bortezomib (velcade) carfilzomib belongs to a class of drugs called “proteasome inhibitors”, however it is felt to be possible more potent than bortezomib as it causes irreversible inhibition of the proteasome. It is given by intravenous injection and in this study it was given on days 1,2,8,9,15,16 of a 28-day cycle in addition to lenalidomide and dexamethasone. Patients who received KRd had higher responses rates than those who received Rd only – 87% versus 67%, with more complete responses in the KRd group. In addition the average time to myeloma progression following KRd was 26.3 months compared to 17.6 months for Rd. Prior to this study there have been some concerns about possible cardiac side-effects related to carfilzomib in earlier-phase clinical trials, however in this trial KRd was very well tolerated with no significant differences in toxicity between KRd and Rd groups. Overall, the results of this trial were felt to be very encouraging, particularly the very high overall response rate and long progression free survival with KRd.
2. Abstract 84: 84 Safety and Efficacy of Daratumumab with Lenalidomide and Dexamethasone in Relapsed or Relapsed, Refractory Multiple Myeloma (T Plesner et al)
This next study again focused on the treatment of relapsed myeloma. In this smaller study, patients with relapsed myeloma again received lenalidomide and dexamethasone (Rd) but this time in combination with a new myeloma drug called daratumumab. Daratumumab belongs to a class of drugs termed “monoclonal antibodies”. These antibodies bind to a target on a cancer cell and in the case of daratumumab the target is CD38 which is a protein which is present in large amounts on myeloma cells but not on many other cells in the body.
The binding of daratumumab to CD38 ultimately leads to myeloma cell death through a combination of mechanisms. To date this trial has included 45 patients and the 3-drug combination has led to very high response rate of approximately 90%. Overall, the 3-drug combination was well tolerated and plans are now afoot to explore daratumumab-based combinations in newly diagnosed myeloma and in larger studies.
3. Abstract 82: Long-Term Ixazomib Maintenance Is Tolerable and Improves Depth of Response Following Ixazomib-Lenalidomide-Dexamethasone Induction in Patients (Pts) with Previously Untreated Multiple Myeloma (MM): Phase 2 Study Results (S Kumar et al)
This next study explored the effectiveness of another new anti-myeloma drug, ixazomib, again in combination with lenalidomide and dexamethasone in patients with newly diagnosed myeloma. Ixazomib, like bortezomib and carfilzomib, is a proteasome inhibitor but unlike these agents which are given by intravenous or subcutaneous injection, ixazomib is given in tablet form. This treatment approach should offer significant benefits for patients (no injections, less day-ward visits) and hospitals. Preliminary results from this study were presented at the 2013 ASH meeting and this treatment regimen resulted in a 95% overall response rate. The data presented at the 2014 meeting focused on those patients who received ixazomib as a maintenance treatment i.e. to maintain the response to treatment.
Forty-three percent of 49 patients went on to receive ixazomib maintenance treatment, with 48% percent of these patients improving their overall response. The combined rate of complete and near complete responses increased from 24% after induction to 62% after maintenance treatment. Importantly, the maintenance treatment was well tolerated with just 10% of patients requiring a dose reduction during the maintenance phase of the study.
The introduction of a highly active oral proteasome inhibitor should prove to be a major advance in myeloma treatment.
4. Abstract 80 Safety and Efficacy in the Stratus (MM-010) Trial, a Single-Arm Phase 3b Study Evaluating Pomalidomide + Low-Dose Dexamethasone in Patients with Refractory or Relapsed and Refractory Multiple Myeloma (M Dimopoulos et al)
The next study examined the effect of a new anti-myeloma drug, pomalidomide, in combination with dexamethasone in myeloma patients who received many lines of treatment and whose disease was now at a refractory stage. Pomalidomide belongs to a class of drugs called immunomodulators, which also includes thalidomide and lenalidomide (revlimid). In total 604 patients were enrolled in this study (including some myeloma patients from Ireland). These patients had received an average of 5 prior lines of treatment
and all had received both lenalidomide and bortezomib with almost 80% being refractory to both agents. In total, 35% of patients responded with a median progression-free survival of 4.2 months. The median overall survival was 11.9 months which was an encouraging result in myeloma patients who in essence have stopped responding to all other anti-myeloma therapies. These results are in line with the results of previous pomalidomide studies and help confirm pomalidomide’s place in the treatment of relapsed/refractory myeloma.