We are inundated with snippets of news from a host of clinical studies reporting interesting (and even exciting) results for us, myeloma patients. The caveat with all those snippets is that they tend to come from early study results (preclinical or Phase I – dose ranging/safety studies) or from Phase II studies with limited numbers of patients and short-term follow-up outcomes. At times, it is good to step back and be aware of the long-term outcomes from the current, FDA approved products in the MM treatment armamentarium.

A recent issue of the Journal of Clinical Oncology reports long-term follow-up data of the largest group (1,000 consecutive newly diagnosed MM patients) treated with the combination Revlimid-Velcade-dexamethasone (also known as RVd). Most of us MM patients will be familiar with this three-drug regimen. The study included both transplant-eligible and non-transplant-eligible patients. Let’s look at the make-up statistics of this patient pool: 

• The median patient age was 61.21 years (range, 16.32-83.05);
• 54.6% were male; 63.3% had standard-risk cytogenetics;
• 25.1% had high-risk cytogenetics;
• The median duration of induction therapy was 3.91 months and the median number of RVD cycles received was 4;
• The median time from diagnosis to stem cell transplant was 5.52 months;
• Among patients who received transplant, 75.1% had upfront ASCT and 16.8% had deferred ASCT.

The results are impressive!

• “The overall response rate was 97.1% after induction therapy and 98.5% after transplantation, with 89.9% of patients achieving a very good partial response (VGPR) or better and 33.3% achieving stringent complete response after transplantation at a median follow-up time of 67 months. 
• The estimated median progression-free survival time was 65 months (95% CI, 58.7 to 71.3 months) for the entire cohort, 40.3 months (95% CI, 33.5 to 47 months) for high-risk patients, and 76.5 months (95% CI, 66.9 to 86.2 months) for standard-risk patients. 
• The median overall survival (OS) time for the entire cohort was 126.6 months (95% CI, 113.3 to 139.8 months). 
• The median OS for high-risk patients was 78.2 months (95% CI, 62.2 to 94.2 months), whereas it has not been reached for standard-risk patients. Five-year OS rates for high-risk and standard-risk patients were 57% and 81%, respectively, and the 10-year OS rates were 29% and 58%, respectively.”

The authors of the journal article draw two key conclusions :

• “RVD is an induction regimen that delivers high response rates (VGPR or better) in close to 90% of patients after transplantation, and risk-adapted maintenance can deliver unprecedented long-term outcomes.” [emphasis added]
• “This study  […] demonstrates the ability of 3-drug induction regimens in patients with newly diagnosed multiple myeloma to result in a substantial survival benefit.”  [emphasis added]

And there you have it : the regimen that most of us are familiar with is a good way to start and continue. Some of us, however, will relapse and some of us will become refractory to any of the drugs used in this combo. That’s when other drugs will enter into the mix and we have options available, not only with different immunomodulators (such as Pomalyst instead of Revlimid), different proteasome inhibitors (such as Kyprolis) and also the addition of biologicals (such as Darzalex).

In 2014, I was told by my specialist, “We have a good program for starters and what we will try and do is buy time. There are exciting developments in the near-term horizon that will give us good options and alternatives in the future.” And she absolutely right. I have an opinion about the cost of RVd but, I will also be the first to admit that this regimen has bought me almost 6 ½ years of high-quality life. Ergo, I don’t complain much about RVd (in my own opinion, of course).