"The maintenance issue is the most important part of these updates, in my opinion," said George Somlo, MD, director of the MML Program at the City of Hope Comprehensive Cancer Center in Duarte, California.
"I don't think we know yet the best maintenance therapy but, based on the most recent data available from randomized studies, lenalidomide seems to be the tool to accomplish optimal maintenance," Dr. Somlo told Medscape Oncology.
It's proven to be safe and effective in patients on different continents and is relatively nontoxic. To me, this has become a major strategy," he added.Although the recommendation to use lenalinomide for maintenance therapy is currently based on level 2A evidence, Dr. Somlo reported that it wasn't because of any disagreements among the panel. Instead, "these results have not undergone full peer review, and safety/efficacy data are still preliminary," reads a new footnote in the updates.
New Induction Therapy Classifications
The NCCN MML guideline updates also introduce new categories for several induction-therapy combinations.
"We have new combinations of novel agents now being tested in prospective randomized studies, allowing us to recommend them as options to accomplish a complete response," explained Dr. Somlo.
He noted that bortezomib plus dexamethasone or doxorubicin or thalidomide for transplant candidates and lenalidomide plus dexamethasone for both transplant and nontransplant candidates are all potential treatment options — and are now included as recommendations for induction therapy, on the basis of category 1 evidence.
Dr. Somlo added that other drugs are coming "down the pipeline" in both the induction and maintenance phases, although these still need to be tested further.
Downgrading Older Regimens
Several older induction regimens have been downgraded this year, from category 2A to category 2B recommendations. These include dexamethasone alone and with thalidomide for transplant and nontransplant candidates; the combination of liposomal doxorubicin, vincristine, and dexamethasone for transplant candidates; and the combination of vincristine, doxorubicin, and dexamethasone for nontransplant candidates.
"I think this shows that it's important to not just rely on older, less effective treatments, but to really consider novel treatment regimens," said Dr. Somlo.
"I don't think we should just look at [MML] as a disease in which we can't really gain long-term survival," he said. "Instead of looking at it defensively, we need to look at it as something we can render into 10, 15 years of survival for our patients down the road. The timeline needs to be pushed further and the strategies of treatment and getting them to the maintenance stage need to be more aggressive."
"Do it like you mean it," Dr. Somlo told the audience, smiling as he spoke.
However, he noted that having novel drug combinations does not necessarily negate the need for autologous or allogeneic stem-cell transplantation. "There absolutely has to be a comparative analysis done and then a figuring out of how we can best use our tools in sequence."
This emphasizes the need for physicians to participate in or refer patients for clinical trials, especially at the national and international levels, said Dr. Somlo. "I would encourage participation because it results in us learning more, patients will benefit, and the next generation of physicians and patients will do better."
Exciting New Array of Treatments
"I think the past few years have been very interesting in MML, with multiple new agents active against the disease coming on line," said William Vaughan, MD, professor of medicine at the University of Alabama in Birmingham and past chair of the NCCN board of directors.
"The challenge is that there are a lot of phase 2-type trials out there and there's a sort of difficulty identifying what standard to use as a control in evaluating new agents," added Dr. Vaughan. "There's also a fair amount of confusion in the literature and I think the NCCN Myeloma Working Group did a great job of trying to separate the wheat from the chaff."
He noted that although aggressive treatment might be a good idea for some patients, it might not work as well for patients with a lot of comorbidities or who present with renal failure because of a higher mortality risk. "So you need to make a decision as to what treatments to discuss with your patients based on their particular situation."
Dr. Vaughan said that this doesn't mean that clinicians need to treat every patient with a different regimen. "By using a regimen, you get better at it as you gain experience and the patients get better."
"However, the field is evolving and there is an exciting new array of treatments and treatment strategies. Physicians in practice need to stay current on this and perhaps talk with their colleagues in their regional NCCN center to get some advice on how to best introduce new therapies into their practice," he concluded.
Dr. Somlo reports receiving grant/research support from AstraZeneca Pharmaceuticals and Pfizer Inc; and working as a consultant and serving on the product/speaker's bureau for AstraZeneca, Genentech, and Novartis Pharmaceuticals Corporation.
National Comprehensive Cancer Network (NCCN) 15th Annual Conference. Presented March 12, 2010.
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