BY GARY PETERSEN
Three recent publications on treatments for newly diagnosed patients have caught my attention. The first of which is the French Myeloma Intergroup study. This multi-center trial of RVD (Revlimid, Velcade, and Dex) with Transplant, RVD Consolidation, and Revlimid maintenance showed exceptional results for newly diagnosed patients. With a median follow-up of 39 months, estimated 3-year progression-free and overall survival were 77% and 100%. Overall, 58% of patients achieved complete response, and 68% were minimal residual disease (MRD) negative by flow cytometry. The survival of 100% is remarkable in comparison to the SEER data which has a 64% survival rate.
The second publication is the University of Chicago (Dr. Jakubowiak) study. This is a multi-center study of Carfilzomib (Kyprolis), Lenalidomide, and low dose dexamethasone for newly diagnosed patients. KRd provided a high rate of sCR (55%) in NDMM patients and 3-year progression-free survival and OS rates of 79% and 96%. Relative survival would therefore be 101.8% vs. the SEER relative survival of 64%. This is a truly remarkable performance in that the 3 year survival is greater than that of the average person at age 69. The study was expanded to further improve response and outcomes, by designed a phase II study to assess activity of extended treatment with KRd induction, ASCT, KRd consolidation, and KRd maintenance. With a medium followup of just 9.7 months, the results are not seasoned but still outstanding. Response improved with each phase of treatment and at the end of 8 cycles, 15/17 evaluable patients (88%) were MRD-negative, all patients were alive and 52 of 53 progression free. KRd with ASCT for newly diagnosed patients resulted in higher sCR rates than KRd without ASCT and high rate of MRD-negative disease, suggestive of benefit of adding ASCT to KRd treatment.
Why is this so remarkable? It is because of how it compares to the recent Blood publication about the Total Therapy program at UAMS in Little Rock. Little Rock has some of the best survival rates and most seasoned data based on the their analysis of the various Total Therapy protocols. For example the 3 year relative survival for TT3, the newest and best performing Total Therapy program was 90.8%. The 3 year survival for the RVD with SCT study, and with KRd without transplant are both better than the TT3 results. The 3 year survival performance of KRd with SCT is expected to be the best of all of these trials. So early results are better than those for TT3, and TT3 has show a cure rate of 50% for all patients. So if the new studies can maintain DURABLE responses, one might expect a similar or better cure rate. This is a huge IF! But let us look at the history of the UAMS Total Therapy program.
- Total Therapy 1 was the baseline and showed a 10% rate of cure and used VAD and dual transplants as the base of the protocolTotal Therapy 2 - T added consolidation and had a 5% improvement in the number of patients cured.
- Total Therapy 2 + T added thalidomide an IMID to the mix and had a 15% improvement in the number of patients cured.
- Total Therapy 3 added bortezomib, a proteasome inhibitor, to the mix and had a 20% improvement in the number of patients cured.
In the conclusion section of this Blood publication it stated the following:
"High CR rates comparable to those achieved with more toxic autotransplant-supported high-dose melphalan have recently been reported with the sole use of novel-agent combinations. Whether these different therapeutic approaches result in equally durable CR, longer follow-up is required. In the interim, we are concerned about prematurely abandoning transplants in favor of therapy solely based on novel agents."
The significant improvement of the KRd + transplant over the KRd alone seems to confirm the continued benefit of transplant leading to the most successful outcomes. So the big question is that of durability. But I would hope because consolidation, the addition of IMID's, and Proteasome Inhibitors to transplant had resulted in the lion share of survival improvement, along with the high rate of MRD (minimum residual disease) negative patients, this would bode well for the durability of these new clinical trials. I hope and pray it does, and TT3 cure rates of 50% can be achieved with less toxicity. As a point of note, a new clinical trial at UAMS will add Kyprolis to the Total Therapy mix, so you can expect continued improvement in the exceptional UAMS survival rate performance.
about the author
Gary is a myeloma survivor and patient advocate. His work centers around helping patients live longer by helping them to find facilities who are beating the average survival statistics. You can find Gary's site at www.myelomasurvival.com and follow him on Twitter at @grpetersen1