Achievement of Complete Response Is Important for Longer Overall Survival in Patients with Newly Diagnosed Myeloma: A Single-Institutional Study

Even with the introduction of novel therapeutic agents, including thalidomide, bortezomib, and lenalidomide, multiple myeloma (MM) is an incurable disease. Deeper responses, such as complete response (CR) and very good partial response (VGPR), are major goals of treatment to obtain long-term overall response (OS) and progression-free response (PSF) in patients with MM. Recent large randomized retrospective studies also suggested improved OS and PFS in patients who achieved deeper responses. However, the prognostic impact of achieving CR or VGPR remains controversial. In addition, these studies included selected patients that may not be representative of the general population. Therefore, we analyzed cases in our database to evaluate the impact of treatment response on the outcome of consecutive patients with symptomatic MM who were treated with chemotherapeutic regimens containing novel agents over the past 6 years at our institution in Kamogawa City, Japan.

We included 97 consecutive patients treated at our institution between April 2005 and May 2011. The study population consisted of 56 male and 41 female patients with a median age of 70 years old (range: 45 −90). Due to the rapid changes in treatment modality and government approval of novel agents in myeloma during this period, initial treatment could not be uniformly categorized, but all patients received chemotherapy regimens containing at least one novel agent, including thalidomide, bortezomib, and lenalidomide. These patients were thought to be more representative of the general myeloma population. Seventy-seven (79.4%), 27 (38.6%), and 55 (56.7%) patients received bortezomib-, lenalidomide-, and thalidomide-containing regimens, respectively. Treatment responses were assessed using the International Myeloma Working Group (IMWG) criteria with minor modifications, and the best response to treatment during the course of disease was evaluated. Immunofixation test and serum free light chain measurements were performed for confirmation of CR and stringent CR. OS was calculated from the time of diagnosis until the date of death from any cause or the date on which the patient was last known to be alive. Univariate and multivariate analyses were performed for the following variables: age at diagnosis, International Staging System (ISS), and best response achieved.

The median age of patients was 71 y.o. (range: 49 −90 y.o.), and the male to female ratio was 56:41. The best responses to treatment were as follows: CR was obtained in 19 cases (19.6%), VGPR in 29 (29.9%), partial response (PR) in 34 (35.0%), and stable disease (SD) or less in 15 (15.4%). Baseline characteristics according to best response achieved in patients who achieved CR, VGPR, PR, and SD or less were similar among the patients ≥70 y.o. vs. ≤70 y.o. Patients' age has no impact on the response to treatment. With a median follow-up of 25 months, Kaplan–Meier estimated 3-year and 5-year overall survival (OS) rates were 67.2% and 35.0%, respectively. The 3- and 5-year OS were 100% in patients with CR, which were significantly superior in patients with VGPR (3-y 70%, 5-y 55.0%) and PR (3-y 60%, 5-y 23.0%). The 3- and 5-year OS were not significantly different between patients with VGPR and PR. Normalization of FLC kappa/Lambda ratio was observed in 15 of 19 (80%) patients with CR, 15 of 29 (51%) with VGPR, 4 of 34 (6.6%) in PR, and in none of 15 (0%) in SD or less. Patients who showed normalization of FLC kappa/Lambda ratio had significant OS benefit compared to those who did not. Proportional hazard Cox models showed that patients with ISS stage I/II had better 5-year OS rate compared to patients with stage III (51%; 20%, P = 0.005). However, there was no association between ISS stage and achievement of CR.

The results of the present study highlighted the importance of achieving CR, not PR or VGPR, and normalization of FLC kappa/Lambda ratio for obtaining long-term OS in patients with MM regardless of age or ISS stage.

No relevant conflicts of interest to declare.