1q gain (+1q) is the most common high-risk cytogenetic abnormality (HRCA) in patients with multiple myeloma (MM). However, its prognostic value remains unclear in the era of novel agents. Here, we retrospectively analyzed the impact of +1q on the outcomes of 934 patients newly diagnosed with MM. +1q was identified in 53.1% of patients and verified as an independent variate for inferior overall survival (OS) (hazard ratio, 1.400; 95% confidence interval, 1.097-1.787; p = .007).Concurrence of other HRCAs (particularly t(14;16) and del(17p)) further exacerbated the outcomes of patients with +1q, suggesting prognostic heterogeneity. Thus, a risk-scoring algorithm based on four risk variates (t(14;16), hypercalcemia, ISS III, and high LDH) was developed to estimate the outcomes of patients with +1q. Of the patients, 376 evaluable patients with +1q were re-stratified into low (31.6%), intermediate (61.7%), and high risk (6.7%) groups, with significantly different progression-free survival and OS (p < .0001), in association with early relapse of the disease. The prognostic value of this model was validated in the CoMMpass cohort.While attaining undetectable MRD largely circumvented the adverse impact of +1q, it scarcely ameliorated the outcome of the patients with high risk, who likely represent a subset of patients with extremely poor survival. Hence, patients with +1q are a heterogeneous group of high-risk patients, therefore underlining the necessity for their Peiyu Yang and Haimin Chen contributed equally to this study.

The Second Revision of the International Staging System (R2‐ISS) was recently introduced to improve risk stratification over that provided by the extensively applied standard revised International Staging System (R‐ISS). In addition to the variables included in the R‐ISS, the R2‐ISS incorporates chromosome 1q gain/amplification and divides the patients into 4 groups with different survival outcomes, better stratifying patients within the R‐ISS intermediate‐risk. The new model was developed based on a great quantity of data from patients participating in uniform clinical trials and has not been validated in real‐world clinical practice. Therefore, we retrospectively analyzed the prognostic value of the R2‐ISS in 474 consecutive patients with multiple myeloma receiving immunomodulatory drugs or proteasome inhibitor‐based regimens as their first‐line treatment. According to the R2‐ISS, 41 (8.6%), 76 (16%), 275 (58%), and 82 (17.3%) patients were identified as R2‐ISS I, R2‐ISS II, R2‐ISS III, and R2‐ISS IV, respectively. The median progression‐free survival (PFS) was 48 (95% CI: 38–58), 35 (95% CI: 23–47), 24 (95% CI: 21–27), and 12 (95% CI: 7–17) months, and the estimated median overall survival (OS) was 110 (95% CI: 42–178), 88 (95% CI: 75–101), 50 (95% CI: 43–57), and 26 (95% CI: 19–33) months (p < 0.001) in the 4 groups, respectively. The R2‐ISS could also classify groups with distinct survival among patients with renal impairment or classified as R‐ISS II. Adjusted by age, sex, treatment approaches and transplantation status, the R2‐ISS was an independent prognostic factor associated with OS with a hazard ratio of 7.055 (95% CI: 3.626–13.726) (p < 0.001) for R2‐ISS IV versus R2‐ISS I and 2.707 (95% CI: 1.436–5.103) (p = 0.002) for R2‐ISS III versus R2‐ISS I. In conclusion, our results suggest that the R2‐ISS is a simple and robust risk stratification tool for patients with multiple myeloma treated with novel drugs and could be used in everyday clinical practice.

Background/objectiveWe retrospectively analyzed the effective and safety of continuous low-dose cyclophosphamide combined with prednisone (CP) in relapsed and refractory multiple myeloma (RRMM) patients with severe complications.MethodsA total of 130 RRMM patients with severe complications were enrolled in this study, among which 41 patients were further given bortezomib, lenalidomide, thalidomide or ixazomib on the basis of CP regimen (CP+X group). The response to therapy, adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were recorded.ResultsAmong the 130 patients, 128 patients received therapeutic response assessment, with a complete remission rate (CRR) and objective response rate (ORR) of 4.7% and 58.6%, respectively. The median OS and PFS time were (38.0 ± 3.6) and (22.9±5.2) months, respectively. The most common AEs were hyperglycemia (7.7%), pneumonia (6.2%) and Cushing’s syndrome (5.4%). In addition, we found the pro-BNP/BNP level was obviously decreased while the LVEF (left ventricular ejection fraction) was increased in RRMM patients following CP treatment as compared with those before treatment. Furthermore, CP+X regimen further improved the CRR compared with that before receiving the CP+X regimen (24.4% vs. 2.4%, P=0.007). Also, both the OS and PFS rates were significantly elevated in patients received CP+X regimen following CP regimen as compared with the patients received CP regimen only.ConclusionThis study demonstrates the metronomic chemotherapy regimen of CP is effective to RRMM patients with severe complications.

No abstract