Individually Tailored Treatment Strategies For Frail Myeloma Patients In Japan
Authors: Ogawa Ryosuke , Ohta Takanori , Aoki Kenichi , Kusumoto Hirotake , Minami Mariko , Higuchi Masakazu , Sugio Yasuhiro , Ohno Yuju 
Published: October 2019

Abstract

Background
Historically, treatment decision of multiple myeloma (MM) has been largely based on age, and elderly patients with comorbidities are often excluded from clinical trials. Although tailored therapy is implicated to be inevitable for these patients, no data are available that account for assessing vulnerability of MM patients, especially of elderly. In order to explore a useful index to screen patients with Japanese MM patients leading to a proper individualized therapy based on our daily clinical practice, we analyzed our local urban area patients.

Methods
We conducted a retrospective analysis of 77 patients (40 male, 37 female) who were diagnosed between June 2009 and November 2012 in two core hospitals in Kitakyushu city. Patients were stratified by age (<65, 65-75 or >75 years), ISS (1, 2 or 3) and FCI (0, 1 or ≥2) consisting of renal impairment, pulmonary disease and performance status.

Results
The median PFS and OS are not significantly different among patients aged <65, 65-75 or >75 years. The median OS of patients with ISS = 1 and 2 was significantly better than that with ISS = 3 patients (525, 583 and 319 days, respectively; p = 0.03, 0.04), but there was no significant difference between ISS = 1 and 2. These indicate that age and ISS are not applicable to prognostic prediction by themselves for MM patients in the novel agent era. When patients were stratified by FCI, 36 out of 77 patients were subdivided into FCI = 0, 35 into FCI = 1, and 6 into FCI ≥ 2. Combination of three risk factors identified significantly different median OS between FCI = 0 and FCI=1 (533 and 377 days; p = 0.03). Significance was alsofound in PFS between FCI = 0 and FCI = 1 (p = 0.02) and between FCI = 0 and FCI ≥ 2 (p = 0.01). When we examined factors involved in FCI in detail, KPS, rather than renal or pulmonary dysfunction, was found to be a more reliable prognostic factor of FCI.
Then we examined prospectively to verify the applicability of this result. An 88-year-old Japanese woman was referred to our institute with a left-sided bone pain with fever. Disease stage was stage II according to the ISS. FCI score was 0, assessed by KPS, renal function and pulmonary function. She was first treated by MP (melphalan of 8 mg/day and prednisone or 30 mg/day) according to a conventional strategy based on age, but this regimen was unsuccessful because of refractoriness. Then she received 10 mg/day of Lenelidomide and 20 mg/day of dexamethasone. The clinical symptoms were improved during the first cycle of Len+Dex treatment. This result indicates the importance of quantifying frailty for clinical management of MM.

Conclusion
In this study we provide an evidence for the utilization of comorbidity assessment in MM patients and facilitate treatment, in the extent of retrospective analysis. We suggest that assessing the frailty, rather than chronological age alone, may allow us to better define each patient’s condition and tolerability for the treatment. Deciding treatment strategy of patients with MM inthe era of novel agents, we recommend considering patient’s frailty which intensely influences patient treatment outcome, and we are eager to develop a simple and powerful method for estimating frailty which can be utilized in our busy clinical practice, named as Kyushu Comorbidity Index (KCI).

Disclosures:
No relevant conflicts of interest to declare.