The prognostic role of 1q21 gain/amplification in newly diagnosed multiple myeloma: The faster, the worse.

BACKGROUND: The prognostic value of additional copies of chromosome 1q (1q gain/amplification [amp]) in multiple myeloma (MM) remains controversial. In the meantime, the kinetics of the response to MM therapy has long been an area of debate. Few studies have pointed out the relationship of response kinetics with cytogenetic abnormalities (CAs) in MM. METHODS: The authors retrospectively analyzed the data of 1068 real-world newly diagnosed MM patients from a Chinese national medical center. RESULTS: Overall, 405 (51.9%) patients had 1q gain/amp, with aggressive clinical characteristics and significant inferior survival. The variation in copy number (CN) of 1q (CN = 3 or CN >3) had no significant impact on the survival of MM patients with 1q abnormalities. No difference was found in the outcome of 1q gain/amp patients treated with doublet or triplet regimens. Upfront autologous stem cell transplantation could eliminate the adverse prognostic effect of 1q gain but not 1q amp. The duration from diagnosis to the first time achieving very good partial response (VGPR) or better was significantly shorter in patients with 1q gain/amp (77 days vs. 100 days, p = .001). Finally, multifactor regression analysis was performed to construct a new risk stratification model in MM patients with 1q gain/amp, which was validated in the Multiple Myeloma Research Foundation CoMMpass study cohort and worked better than the Revised International Staging System and Second Revision of the International Staging System (Harrell's concordance index: 0.631 vs. 0.598 and 0.537). CONCLUSIONS: In the setting of novel therapy, 1q gain/amp still acts as an independent adverse prognostic factor. Patients with 1q gain/amp achieved VGPR rapidly but had inferior survival.

Real world outcomes of lenalidomide or bortezomib maintenance in patients with multiple myeloma not undergoing stem cell transplantation.

Maintenance is one form of long-term therapies in multiple myeloma (MM). Lenalidomide and bortezomib are two commonly used options. The role of maintenance in patients not undergoing transplant remains unclear. A total of 248 newly diagnosed MM patients who received over 180 days of any standard-of-care induction therapy and did not receive autologous stem cell transplantation were included. Patients either receive lenalidomide, bortezomib or no maintenance. Patterns of usage, survival benefit, discontinuation status were analyzed. 93, 99 and 56 patients received no, lenalidomide (Len) and bortezomib (Bor) maintenance respectively. Patients receiving Bor had a higher incidence of traditional high-risk cytogenetics (14.0% (No) vs 14.1% (Len) vs 41.1% (Bor), P < 0.001). Len maintenance conferred a superior progression-free survival (PFS) and overall survival (OS) compared to no maintenance (median PFS, 60.1 vs 26.9 months, P = 0.003; median OS, NR vs 56.7 months, P = 0.046), with a near independent impact on PFS (adjusted HR 0.580, P = 0.058). The PFS and OS benefit of Len maintenance was seen in subgroups of ISS stage I/II, traditional standard-risk cytogenetics, and pre-maintenance < CR. Bor maintenance did not confer PFS or OS benefit for the entire cohort, but improved OS in patients with pre-maintenance < CR. Discontinuation due to toxicity was recorded in 11.1% and 8.9% of patients receiving Len or Bor maintenance respectively. Our study supports lenalidomide maintenance as the standard-of-care in MM patients not undergoing transplant. Further studies are warranted for bortezomib maintenance in the non-transplant setting, and better maintenance strategy is needed for patients with adverse prognostic factors.

The evolving diagnosis and treatment paradigms of multiple myeloma in China: 15 years' experience of 1256 patients in a national medical center.

BACKGROUND: Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. METHODS: We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first-line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. RESULTS: Of the 1256 individuals, median age was 64 (range 31-89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light-chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high-risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short- and long-term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7 months. Advanced ISS stage, HRCA, light-chain amyloidosis and EMD independently predicted an inferior PFS. First-line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light-chain amyloidosis, and receiving PI/IMiD-based regimen versus PI+IMiD-based regimen independently indicated a poorer OS. CONCLUSIONS: In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field.

Clinical profiles in multiple myeloma patients with extreme survivals: a study from a National Medical Center in China.

OBJECTIVES: The clinical outcomes of multiple myeloma (MM) patients are highly variable in the real-world setting. Some MM patients may have clinical endings that do not abide by the book. We aim to describe features of MM patients with extreme survivals in real-world practice. METHODS: This retrospective study enrolled 941 patients consecutively visited a national medical center, China, between July 1995 and December 2021. Among patients, we identified two groups of MM patients with extreme survivals, 56 were in the long-term remission (LR) group with progression-free survival (PFS) ≥ 60 months, and 82 were in the rapid progression (RP) group with PFS ≤ 6 months. RESULTS: CRAB features, of which hypercalcemia, renal insufficiency, and anemia were more common in the RP group, except for bone disease, with a comparable incidence at diagnosis in both groups (88.8 vs 85.7%, P = 0.52). High-risk cytogenetics was detected in 45.7% of patients in the RP group. Of note, 14.3% of MM patients in the LR group harbored del (17p). According to the Revised International Staging System (R-ISS), 9% of patients belonged to stage I in the RP group, and 19% of patients in the LR group were found in stage III. There were 8 (15.7%) patients in the LR group only achieved partial response (PR) as the best response. Median time to best response (TBR) for LR and RP group patients was 4.6 and 1.4 months, respectively. CONCLUSIONS: The disparities in the survivals of MM patients indicated that some unexpected factors have influenced the outcomes in the real-world setting.

Update on the outcome of M-protein screening program of multiple myeloma in China: A 7-year cohort study.

BACKGROUND: To improve the early detection rate of multiple myeloma (MM), the M-protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based monoclonal immunoglobulin (M-protein) screening integrated into the blood biochemistry panel. This study updated 7-year follow-up findings of MM patients diagnosed by screening-driven and symptom-driven approaches. METHODS: The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening-driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma-related end-organ damage were categorized into the symptom-driven group. RESULTS: There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening-driven group, while 545 were to the symptom-driven group. Compared to the symptom-driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease-related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression-free survival (PFS) than the symptom-driven group (62.2 vs. 24.9 months, p < 0.001, HR: 2.12, 95% CIs: 1.69-2.65), with median follow-ups of 32.6 and 27.4 months. Furthermore, the median overall survival (OS) was significantly longer in patients of the screening group (not reached vs. 62.3 months, p < 0.001, HR: 2.49, 95% CIs: 1.81-3.41). After being adjusted for well-acknowledged myeloma prognostic factors, the screening-driven diagnostic pattern remained an independent prognostic factor indicating improved PFS and OS in MM patients. CONCLUSION: Routine M-protein screening for MM in the hospital population results in an earlier diagnosis and better patient outcomes.