Risk profile predicts survival in transplant-ineligible multiple myeloma

By Marilynn Larkin

NEW YORK (Reuters Health) - 21/2/2019

In patients with multiple myeloma who are ineligible for stem-cell transplantation, the UK Myeloma Research Alliance Risk Profile (MRP) predicts overall survival across treatments and genetic factors, researchers say.

Dr. Gordon Cook of the University of Leeds in the UK told Reuters Health by email, "Tolerability of anti-cancer therapy can limit treatment, affecting disease response and survival. There is a need for an objective risk score, possibly incorporating frailty biomarkers."

Dr. Cook and colleagues developed the MRP using data from two randomized controlled trials of patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. The trials were the NCRI Myeloma XI (NCRI-XI) study, which included 1,852 patients, and the MRC Myeloma IX (MRC-IX) study, which included 520.

The profile's prognostic variables include WHO performance status, International Staging System (ISS) stage, age, and C-reactive protein concentration.

As reported online February 6 in The Lancet Haematology, MRP group designation - low, medium or high risk - was associated with overall and progression-free survival in both trials.

The groups also predicted early mortality with good discriminative ability in both studies, with areas under the receiver operating characteristic curve of 0.72 for the NCRI-XI and 0.66 for the MRC-IX.

With low-risk patients as the reference group, the odds ratios for early mortality were 2.14 for medium-risk patients and 4.76 for high-risk patients in the NCRI-XI; for the MRC-IX, ORs were 1.92 for medium-risk patients and 10.59 for high-risk patients.

The median percentage of the induction therapy protocol dose delivered was lower in higher-risk groups. During induction, low-risk patients received 88.57% of the minimum protocol dose, whereas medium-risk patients received 79.63% and high-risk patients, 64.79%.

Further, there was an association with baseline quality of life subscales from commonly used patient-reported outcomes.

The MRP remained prognostic in patients exposed to different therapeutic combinations and in patients with genetic high-risk disease.

"The ability of clinical scoring systems such as the MRP to predict early treatment cessation could enable pre-emptive, upfront dose adjustment, preventing toxicity and potentially enabling patients to stay on therapy for longer," Dr. Cook said.

"All the scoring systems developed to date in myeloma lack an inherent dynamism, making them unable to accommodate any disease-related frailty overlay that is minimized by anti-myeloma therapy," he noted. "There is therefore scope to further improve clinical scoring systems to manage patient-directed therapy."

A study comparing the new risk score with the International Myeloma Working Group Frailty Score in a study will begin in June 2019, according to the authors.

Commenting on the study, Dr. Joshua Richter of the Hematology and Medical Oncology Division of the Tisch Cancer Institute at Mount Sinai in New York City, said the MRP "is a great bedside clinical tool to evaluate newly diagnosed myeloma patients regarding risk stratification as it applies to overall survival."

"There are a variety of predictive models and tools available in the myeloma world," he noted. "However, the benefit of the MRP is the ease of its use and ability to provide insight for prognosis without the availability of a bone marrow or cytogenetic information."

"We can use this tool to have a meaningful discussion about prognosis at an early or even initial visit with a patient without the need to defer the conversation for weeks pending cytogenetics and FISH data," he said. "By incorporating the CRP along with the ISS, the MRP adds tumor biology into an otherwise 'host-centric' viewpoint of performance status and age alone."

That said, the tool has a few limitations, he noted. "The data that this draws from is geared towards 'transplant-ineligible' patients, which may skew factors such as age and performance status in such a way that their effect may be more magnified relative to the impact of cytogenetic risk."

The importance of genetic risk factors led to the development of the revised ISS (R-ISS), he noted. "However, these factors are not accounted for in this model."

Further, he said, "the dataset used for this model involves patients treated with therapies which, while still in use, are not the most current/active therapies."

"It is possible that the more modern therapeutic approaches may obviate the clinical power of this model," Dr. Richter concluded.

In addition to the Medical Research Council, eight pharmaceutical companies contributed funds for the study. Dr. Cook and all but one coauthor have received fees from one or more of the companies.

SOURCE: http://bit.ly/2SiK637 and http://bit.ly/2Sggnrs

Lancet Haematol 2019.

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