NEW YORK CITY—Complete remission would seem to always be the goal in multiple myeloma, but sometimes a CR is overrated.
Angela Dispenzieri, MD, Professor of Medicine, Laboratory Medicine and Pathology at the Mayo Clinic, spoke on response evaluation here at the Lymphoma & Myeloma International Congress on Hematologic Malignancies.
In her presentation, Dr. Dispenzieri said high response rates don't necessarily translate into better overall survival when age and toxicities are also taken into consideration.
“Be cautious in just looking at response as the ultimate endpoint,” she said. “As we look at response we have to look at it in a more complex environment. When we say somebody is in a CR, it's not just the CR, it's what is their biology and who they are—that's going to have a tremendous impact.”
Response evaluation certainly affects treatment approach, she said, “but perhaps a little too much, at the cost of toxicity and severe adverse events.
“Usually the deeper the response, in general, the better the prognosis, but it's not a slam dunk,” she said. “My point is that we focus so much on these little abbreviations and words, and it's so much more complex than that.”
She said often a physician will consult data from clinical trials, graphs with curves depicting regimens and response rates, to help select a treatment.
“You pick the one with the highest CR or VGPR [very good partial response—i.e., a 90% reduction in tumor burden] rates, and that's what you give to your patient. I would argue that this is a little simplistic because it's not accounting for a lot of other variables.”
As an example, Dr. Dispenzieri showed data from a study by the Spanish Group for Malignant Myeloma (GEM2000) and the Program for the Study of Therapy in Malignant Hemopathology (PETHEMA), led by Dr. Juan José (JCO 2008;26:5775-5782).
Dr. Dispenzieri characterized the trial as an amalgamation of patients treated with alkylator-based induction followed by transplant, focusing on responses after induction and after transplant in patients who achieved CR.
“They saw that patients who went into the transplant already in near CR but didn't get upgraded further into a full CR [had a significantly worse prognosis] than those who went into the transplant in a PR and had their response upgraded to a near CR. This gives us a sense that what we call ‘near CR’ isn't always the same. There are a lot of factors that feed into whatever response category we are talking about.”
She said the trial showed a very similar phenomenon with event-free survival.
Another speaker commented on this point in a telephone interview after the meeting. Sergio A. Giralt, MD, Chief of the Adult Bone Marrow Transplant Service at Memorial Sloan-Kettering Cancer Center, agreed that achieving a complete response is sometimes not an ideal outcome.
“There's a point where you get to the laws of diminishing returns,” Dr. Giralt said. “CR should be the surrogate marker for everybody, but once you reach a certain point, pushing towards a CR might not be to the patient's best interest because you buy toxicity but you don't necessarily buy benefit.”
He said about one out of three patients with myeloma now achieve CR prior to transplant.
“Many of us would say that if you are not in CR, the surrogate endpoint, you definitely may benefit from a transplant because it might get you into a CR. Then the question becomes, should you wait until you have a 50%, 90%, or 100% reduction before going to transplant?
“And if you are in a near-CR and I do a transplant and you still don't achieve a CR, do I panic, since there are other things we can look at, like maintenance therapy? At this point we don't know the answer to that.”
Asked about the GEM2000-PETHEMA study, Dr. Giralt noted that the study was retrospective and patients were not treated homogenously.
“I don't think we have totally figured this study] out yet,” he said.