Hesitation still surrounds use of ‘cure’ word in MM

Cure is not simply about having a few patients cured – it’s about reliably being able to cure a population with a disease, argues Professor S Vincent Rajkumar (Mayo Clinic, USA).  Along with Professor Robert Orlowski (MD Anderson Cancer Center, USA), he discusses whether myeloma is an incurable disease or whether it’s just that we don’t yet have the right recipe yet.

Articles by Thomas R Collins. Interviews by Esther Drain.

With technology that allows clinicians to determine minimal residual disease negativity down to the 10^-6 level, the word “cure” hangs in the air — a tantalizing potential addition to the multiple myeloma vocabulary.

But it’s a word that the world’s top researchers and clinicians are still reluctant to use, based on discussions held in a session here before the Annual Meeting of the American Society of Hematology.

Professor Philippe Moreau, MD, head of haematology at University Hospital in Nantes, France, posed the case of a 61-year-old diagnosed with MM and treated with 4 cycles of bortezomib-lenalidomide –dexamethasone, and then achieved a stringent complete response after an autologous stem cell transplant, with MRD to 10^-5. Three years after maintenance therapy, he is at MRD-negative by next-generation flow technology, able to detect disease down to the 10^-6  level.

“Do you consider this patient cured?” Professor Moreau asked.

Most of the experts on the panel said they were “unsure” whether this patient should be characterized as cured.

“Maybe some of them are cured, don’t you think?” said moderator Brian Durie, MD, attending physician at Cedars-Sinai Medical Center and chairman of the International Myeloma Foundation. “Hopefully we’re starting to cure some patents.”

Vincent Rajkumar, MD, professor of haematology at Mayo Clinic, said using the word “cure” now may be using the term too loosely, because “the implications are so huge.”

“The truth is that if I get multiple myeloma — or somebody younger than me, let’s say 40 years old, gets multiple myeloma — can we really look them in the eye and say ‘I can cure you?’” he said. “With a certain percentage of certainty, like we do for diffuse large B cell (lymphoma) or Hodgkin’s disease? No.”

At Mayo, he said, researchers looked at patients treated over the last 10 years who were less than 40, with continuous follow up, and relapse reliably occurred with time.

“Yes, you will be MRD-negative for 5 years but many years need to go by before I know that it’s a curable disease.”

Bruno Paiva, MD, PhD, a hematologist and immunologist at University of Navarra in Spain, said that a more careful characterization is better than the word “cure.”

“When you say there is no disease, you are saying you are not seeing any disease, but eventually there might be some. However, it may be at such a low level that it can be kept under control for several years,” he said. “I think this kind of definition is more appealing than the word ‘cure.’”

Professor Moreau noted that high rates of progression-free survival have been seen at 30 months after maintenance therapy for patients who are both MRD-negative to 10^-6 as well and PET-CT-negative — about 87%, compared about 53% for other patients in a recently published study.¹

“Some patients in this group may be cured when you are looking at progression-free survival data,” he said. “The message here is maybe that we need to look not only within the bone marrow, but also outside the bone marrow, and that the two technologies are probably complementary.”

Reference

1. Moreau P, Attal M, Caillot D, et al. Prospective Evaluation of Magnetic Resonance Imaging and [18F]Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study. J Clin Oncol. 2017 Sep 1;35(25):2911-2918.