IMV 2015: Newly diagnosed multiple myeloma, elderly patients: Professor Gareth Morgan, (Little Rock, USA) and Professor Paul Richardson, (Boston, USA) discuss managing older patients with MM

The majority of patients presenting with MM are elderly and pose a considerable clinical challenge in terms of disease burden and comorbidities compared with their younger counterparts. A plenary session on the management of newly diagnosed elderly MM patients included presentations on the optimal therapy for fit and unfit elderly MM patients, respectively.

Professor Ruben Niesvizky from Weill Cornell Medical College in New York described how elderly MM patients have lagged behind in the dramatic improvement in overall survival seen in recent years.¹ High-risk cytogenetics including t(4;14) and del(17p) appear to have the same negative effect on PFS in elderly patients as in younger patients.² Instead, Professor Niesvizky attributed this lack of improvement in outcomes in the elderly MM population to factors such as the presence of co-morbidities,³ independence and functional status,⁴ and tolerability to treatment,^{5, 6} and stressed the importance of taking these factors into account when making treatment decisions in elderly patients.

The therapeutic goals in fit elderly MM patients are the same as for younger patients, namely to achieve high-quality sustained CR with MRD-negativity, and according to Professor Niesvizky the medical strategies to achieve this should be the same. The use of autologous stem cell transplantation (ASCT) in patients aged 60 years and over has increased in the last two decades with an accompanying significant increase in overall survival in this patient group;^7-11 Professor Niesvizky advised that the decision whether to transplant or not should be based on the patient’s functional/performance status, cardiac, liver and pulmonary function and the presence of any infections, as well as the patient’s own preferences and access to psychosocial support. There is also increasing evidence to support that elderly patients can benefit from novel agents: combination therapy with carfilzomib, lenalidomide and dexamethasone resulted in a 12-month PFS rate of 97% and a 24-month PFS rate of 92% in 23 patients aged 65 years and over, with patients progression-free and alive after a median follow-up period of 13 months.¹² Carfilzomib has also been combined with melphalan and prednisone to patients aged 65 and over with overall response rates of 90% as a result.¹³ Professor Niesvizky speculated that as oral proteasome inhibitors, novel immunomodulators and monoclonal antibodies become available, these will further expand the therapeutic options for fit elderly patients in the future.

Whilst the introduction of novel agents has improved outcomes in elderly patients in clinical trials,^14,15 the benefit is less evident in real-life registry data.¹⁶ Professor Sonja Zweegman from Amsterdam proposed that this reflects treatment of unfit elderly patients who are not eligible for inclusion in clinical trials due to co-morbidities and frailty. The challenge clinicians face is to identify these patients and tailor treatment to optimise efficacy without compromising quality of life. Professor Zweegman stressed that being ‘unfit’ is not simply the same as being old or having a poor performance status; a better way of assessing fitness is frailty. There are tools available for measuring frailty such as the Comprehensive Geriatric Assessment tool, but in a practical setting these are often time-consuming to administer and also not well documented in haematological cancers. IMWG has developed a concise frailty score which is based on age (<75, 75-80 or >80 years, score 0,1 or 2 respectively), the Charlson Comorbidity Index (CCI) (1 or 2, score 0 or 1) and the (instrumental) Activities Daily Life score (ADL >4 or ≤4, score 0 or 1; iADL>5 or ≤5, score 0 or 1), and predicted non-haematological toxicity which was validated in a recent analysis of data from 869 individual newly diagnosed elderly MM patients who had been included in three prospective trials.¹⁷ Patients who were defined as frail (score ≥2) were 1.8 times more likely to discontinue treatment compared with fit patients (score 0). The three-year overall survival rate was 84% in fit patients compared with 57% in frail patients (hazard ratio 3.57; p<0.001). A calculator for this concise frailty score is available at www.myelomafrailtyscorecalculator.net.

In terms of actual treatment strategies for unfit elderly patients, Professor Zweegman pointed to studies which show that the addition of bortezomib or thalidomide to melphalan and prednisone, at doses lower than those used in fit MM patients, can improve overall survival by up to a year.^18-21  Using lenalidomide instead of thalidomide in combination with melphalan and prednisone reduced toxicity with similar^{22, 23} or superior¹⁶ efficacy. Prospective clinical studies in uniform populations are needed to validate the IMWG frailty score and devise dose recommendations for elderly unfit MM patients.

 

Ruben Niesvizky (Weill Cornell Medical College, New York City, USA) and Sonja Zweegman (VU University Medical Center, Amsterdam, the Netherlands)

 

References

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