Newly Diagnosed Multiple Myeloma Patients Research Articles

PB2036: RISK AND PATTERN OF INFECTIONS IN NEWLY DIAGNOSED PATIENTS OF MULTIPLE MYELOMA VACCINATED UPFRONT AGAINST PNEUMOCOCCUS & INFLUENZA

Background: Infections contribute to an early mortality risk of 15 percent in newly diagnosed multiple myeloma(NDMM) cases. There is a limited literature on the type of infections in fully vaccinated NDMM patients. Aims: To study epidemiology, clinical profile and predictors of infection in NDMM who are immunised against pneumococci and influenza. Methods: NDMM patients were prospectively studied for 6 months for the pattern of infections. All patients were vaccinated with pneumococcal and Influenza vaccine at diagnosis. PJP prophylaxis and fluconazole prophylaxis was given for patients receiving high dose steroids while acyclovir was given to all. Infections were classified as microbiologically defined, clinically defined and fever of unknown focus according to definitions published by the International Immunocompromised Host Society. Severity of infections were graded according to the NCI CTCAE Ver5. Results: Forty-eight NDMM patients with a median age 55 years comprising of 26 males and 22 females were enrolled. Renal involvement was noted in 42% of enrolled patients and two third of them required renal replacement therapy. ISSIII and R–ISS III were 70.8 % and 62.5 % respectively. 85% had poor performance status(ECOG ≥2) at baseline. RVD was the most common regimen (37%)used. 6 patients received daratumumab based regimen. Treatment response of atleast VGPR was seen in 97 % of NDMM patients. A total of 19 episodes of infections were observed during 6 months. All episodes of infections were reported in the first 45 of myeloma diagnosis(Median 6 days; Range 0–45). Ten of these episodes of infection were diagnosed during the initial evaluation for myeloma defining events. Microbiological diagnosis was possible in 63 %. Commonest infectious agent was COVID 19(n=8) followed by Gram negative bacteria (n=5) viz E.coli and Klebsiella pneumoniae. None of the eight patients who developed COVID 19 infection had received COVID vaccine as they antedated the operationalisation of national guidelines for immunisation. Respiratory and the urinary tract were the most common focus of infection. All critically ill COVID patients succumbed to progressive respiratory failure and all patients with mild and moderate COVID illness recovered uneventfully. Early mortality in our cohort of forty eight patients was twenty percent(n=10). Three fourths of infections in our cohort were Grade≥3 severity. A total of seven deaths were attributable to infectious diseases in this cohort of NDMM patients. Imune paresis was seen in eighty four percent of patients at diagnosis. On follow up at 6 months; immune paresis had persisted in only thirty seven percent. Regression analysis of variables with odds of infection is shown in Table 1 Baseline BMI<18.5 kg/m2; albumin<3g/dl and ISS or R–ISS stage ≥ 2 was found to be have statistically significant odds of predicting infection risk in the cohort of patients. The choice of myeloma regimen, presence of high risk cytogenetics and response to therapy did not correlate with increased odds of infection in our cohort. Image:Summary/Conclusion: Conclusion In this prospective study of NDMM patients vaccinated against pneumococci and influenza at baseline; infection attributable early mortality was 14.5 %. Advanced stage of presentation, hypoalbuminemia and baseline BMI < 18.5 kg/m2 correlated with increased odds of infection. COVID vaccination and COVID appropriate behavioural practices may mitigate COVID related outcomes including deaths in myeloma patients.

P978: IXAZOMIB VERSUS LENALIDOMIDE OR IXAZOMIB AND LENALIDOMIDE COMBINATION AS MAINTENANCE REGIMEN FOR PATIENTS WITH MULTIPLE MYELOMA: INTERIM ANALYSIS OF A MULTI-CENTER PROSPECTIVE STUDY IN CHINA

Background: Maintenance therapy (MT) deepens response and prolongs progression free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) after frontline regimens. Ixazomib, a 2nd generation oral proteasome inhibitor (PI), has been approved for MT because of its convenience and tolerability. Aims: We conducted this prospective multi-center study to compare the efficacy and safety of Ixazomib (I-MT) or Ixazomib plus Lenalidomide (IL-MT) to Lenalidomide (L-MT) as maintenance regimen in NDMM patients. Methods: This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and registered (NCT04217967). NDMM patients were enrolled from 10 centers of North China MM Registry since September 2019. After 4 cycles of front-line induction therapy, patients reached partial response (PR) would receive autologous stem cell transplantation (ASCT) if eligible, or keep up to 5 cycles of front regimens if ineligible, then start maintenance therapy. Patients did not reach PR would switch to 2nd-line induction for 2-5 cycles and start MT once PR was achieved. For MT, 4mg of Ixazomib was given on day 1,8,15, and 25mg of Lenalidomide every other day on days 1–21 of 28day cycles. Patients in dual drug group were administrated with both Ixazomib and Lenalidomide, dose as listed above. The primary endpoint was PFS from MT. Results: A total of 176 patients were enrolled, including 58 in I-MT, 72 in L-MT and 46 in IL-MT. The demographic and clinical characteristics, including gender ratio, age, paraprotein isotype, ISS, R-ISS, were comparable among different MT regimen groups either receiving ASCT or not at baseline (Table 1). The proportions of patients with high-risk cytogenetic abnormalities (HRCAs), defined as amplification 1q21, deletion 17p, t(4,14) and t(14,16), were lower in L-MT without ASCT and I-MT with ASCT. The median follow-up duration since MT was 10.6, 12.6 and 11.1 months in I-MT, L-MT and IL-MT groups in non-ASCT patients, while 9.3, 14.0 and 12.2 months in ASCT patients, respectively. In non-ASCT groups, the disease progression rates were 13.5%, 10.2% and 10.8%, whereas 0, 21.7% and 0 in ASCT groups. The median PFS and OS were not reached (NR) in all groups. There were 73.1%, 73.4% and 78.3% of the patients reached VGPR or better before MT in non-ASCT patients, while the rates improved to 80.8%, 81.6% and 86.5% during follow-up. The depth of response did not change in ASCT patients. In the whole cohort, the prevalence of peripheral neuropathy (PN) was 18.9% on I-MT, 8.3% on L-MT and 21.7% on IL-MT. Grade 2 PN occurred in 3, 0 and 2 patients, respectively. The incidence of gastrointestinal (GI) events was 12.1%, 1.4% and 15.2%, respectively. Grade 3 GI events occurred in 3, 0 and 1 patients. The incidence of grade 3-4 hematologic toxicities was 1.7%, 4.2%, and 2.2%. Infections developed in 10.3%, 2.8% and 4.3% patients. No drug withdrawal was related to adverse events. Image:Summary/Conclusion: Due to inadequate access to melphalan and low rate of ASCT, the PFS of NDMM in Chinese patients was relatively inferior. We design this multi-centered prospective study to evaluate if dual drug MT will further strengthen response and make up the gap. Though the primary endpoint--PFS has not been reached in all treatment groups, dual MT improves response most and is quite tolerable.

PB2005: BORTEZOMIB, LENALIDOMIDE AND DEXAMETHASONE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS: A REAL-WORLD STUDY OF CHINA

Background: Multiple myeloma (MM) is a hematological malignancy characterized by the malignant proliferation of monoclonal plasma cells. In recent years, a series of new drugs such as proteasome inhibitors, immunomodulatory drugs and autologous hematopoietic stem cell transplantation (ASCT) have been widely used in MM patients and have prolonged the survival of them. Nowadays Bortezomib/lenalidomide/dexamethasone (VRD) is considered as the first-line induction therapy for newly diagnosed multiple myeloma (NDMM) in most clinical guidelines. However the data of VRD in China is insufficient. Aims: To evaluate the efficacy of VRD in NDMM patients as well as the effect of the regimen on the stem cell collection and on the long-term prognosis in the real world. Methods: The clinical characteristics, survival rates, response rates and minimal residual disease (MRD) of 87 NDMM patients at Institute of Hematology & Blood Diseases Hospital from January 1, 2013 to January 1, 2020 were retrospectively analyzed and the impact of lenalidomide on stem cell collection was evaluated. Response was evaluated after 2 courses of induction therapy, before ASCT and at day100 after ASCT. The best response was defined as the deepest response during the follow-up. MRD was evaluated by multiparameter flow cytometry (MFC) with 10-4 sensitivity. Results: The median age of the patients was 56 years old (36-78) and males and females accounted for 58.6% and 41.4%, respectively. The overall response rate (ORR) was 95.9% after 2 courses of induction therapy, with 13.5% achieving the deep response (complete response (CR) or better) and 51.3% of patients achieving a very good partial response (VGPR) or better. After 4 courses of induction therapy, the ORR achieved 95.2%, and the proportions of the deep response and VGPR or better grew up to 46.0% and 77.7%. According to the treatment, the patients were divided into transplantation group and non-transplantation group. After the induction therapy, 88.8% of patients in the transplantation group achieved VGPR or better, and 55.5% reached the deep response. After the transplantation, the proportion increased to 97.2% (P=0.174) and 77.2% (P=0.055), respectively, with the rate of undetectable MRD increasing from 44.4% to 77.8% (P=0.004). In the non-transplantation group, 78.9% of patients achieved VGPR or better after 4 courses of induction therapy, 44.7% of the patients achieved deep response and the rate of undetectable MRD was 42.4%. Compared with the non-transplantation group, transplantation was associated with a higher rate of response (P＜0.001) and a lower rate of MRD detection(78.4% vs 57.1%, P=0.053). The median follow-up time of all patients was 26.3 months (6.2-61.4). The median PFS and OS were not reached. The three-year PFS and OS rates were 82.1% and 87.0%, respectively. None of the standard-risk group, the high-risk group, the transplantation group and non-transplantation group achieved the median PFS and OS. The number of CD34+ positive cells tended to decrease after more than 4 courses of VRD induction therapies. Image:Summary/Conclusion: VRD regimen is highly effective and results in a substantial survival benefit. VRD followed by ASCT is associated with higher rate of deep response, lower rate of undetectable MRD and longer survival.

P876: INCIDENTAL DISCOVERY OF PROBABLE PATHOGENIC GERMLINE VARIANTS IN MULTIPLE MYELOMA PATIENTS UNDERGOING SOMATIC GENOMIC PROFILING

Background: Next-generation sequencing (NGS) is increasingly used to characterize the somatic mutational landscape of patients with multiple myeloma (MM) and guide precision medicine approaches. Somatic genomic profiling (SGP) in cancer patients can lead to the incidental discovery of pathogenic or likely-pathogenic germline variants (PGVs) in ~4% of cases (PMID 26787237). Our previous analysis of whole exome germline data from 895 MM patients in the MMRF CoMMpass dataset showed ~8% of MM patients carry a PGV in a hereditary cancer gene (HCG), and identified shared characteristics among PGV carriers including younger age at diagnosis, higher likelihood of having family history of hematologic malignancy, higher likelihood of t(11;14) MM, and favorable outcomes (Thibaud et al, ASH 2021). Aims: The present study aims to assess the rate of detection of probable PGVs (PPGVs) in MM patients undergoing targeted SGP. Methods: We retrospectively reviewed results of 1,614 commercial NGS panels performed by a single genetic testing laboratory on bone marrow aspirates of 1,095 MM patients treated at our institution since 2015 who were not enrolled in the MMRF CoMMpass study. We considered individual variants to be PPGVs when all of the following criteria were met: 1) variant found in a panel of 106 well-established HCGs (same panel used in our prior study, but excluding TP53 given high rate of somatic mutations in MM); 2) variant unambiguously listed as pathogenic or likely pathogenic (P/LP) in ClinVar, or variant classified as “conflicting interpretations of pathogenicity” but reported by ≥2 CLIA-certified labs as P/LP; 3) variant allele frequency (VAF) >30% (per PMID 33236764); 4) variant detected in all available test reports for a given patient (and VAF >30% in all available test reports). Well known founder variants (FV) in specific populations were labeled as PPGV-FVs. Results: 95 MM patients (8.7%) had a genetic variant meeting criteria to be classified as a PPGV. Two patients had 2 distinct PPGV. PPGV were most commonly detected in the following HCGs (Table 1): APC (n=22), CHEK2 (n=20), ATM (n=7), BRCA1 (n=6), MUTYH (n=6). Of all PPGV carriers, 47 (49%) carried a PPGV-FV. Median VAF for PPGVs was 48.2% (range 30-85%). 34 PPGV carriers had serial NGS tests available (range 2-5 reports); in these patients, VAF standard deviation across serial measurements was <5% in 89% of cases. Taken together, these findings indicate a high likelihood that PPGV detected in these MM patients while undergoing tumor sequencing are indeed incidentally-discovered PGV warranting referral to a genetic counselor for consideration of confirmatory testing. Image:Summary/Conclusion: SGP of bone marrow aspirate in MM patients incidentally detected PPGV in well-established HCG in 8.7% of cases. These findings are consistent with those of our prior study, which found an 8.6% prevalence of PGV in newly-diagnosed MM patients. In MM patients undergoing SGP, detection of a mutation involving a HCG and with a VAF >30% should prompt referral to genetic counseling for confirmatory testing, as PGV detection can have clear implications for patients and their families.

S175: ATLAS: A PHASE 3 RANDOMIZED TRIAL OF CARFILZOMIB, LENALIDOMIDE, AND DEXAMETHASONE VERSUS LENALIDOMIDE ALONE AFTER STEM-CELL TRANSPLANT FOR MULTIPLE MYELOMA

Background: Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), suggesting a benefit of post-ASCT KRd therapy. Aims: We report the results of ATLAS, a multicenter, international, open-label randomized phase 3 study to determine the efficacy and safety of post-ASCT KRD vs standard lenalidomide (R) maintenance (NCT02659293). Methods: Newly-diagnosed MM patients (pts) who received any induction therapy for up to 12 months (mo) followed by single ASCT and achieved at least stable disease within 100 days afterward were randomized to receive either KRd or R, stratified by post-transplant response (≥VGPR vs <VGPR) and cytogenetic risk [standard risk (SR) vs high [HR: presence of t(4;14), t(14;16), or del(17p)]. Pts randomized to KRd received carfilzomib 36 mg/m2 on days (D) 1,2,8,9,15,16 for 4 cycles (C) then D1,2,15,16 starting C5; R 25 mg D1-21, and dexamethasone 20 mg D1,8,15,22 in 28-day cycles. KRd pts with SR who reached IMWG-defined MRD-negativity after C6 de-escalated therapy to R alone after C8 (KRd->R); the rest continued KRd through C36 followed by R alone until progression. Pts randomized to R received lenalidomide 10 mg C1-3 and then 15 mg daily. The primary endpoint was progression free survival (PFS) rate: based on historical PFS rates, a sample size of 180 Pts was calculated to provide 85% power with 2-sided alpha 0.05. Secondary endpoints included minimum residual disease (MRD) negativity response rates and treatment-related adverse events. Results: 180 pts were enrolled (R n=87; KRd n=93) through 10/21/20; data cutoff was 12/31/21. Pt characteristics in the KRd and R arms were balanced for median age (58 vs 59 yrs), ≥VGPR (88% vs 92%), and HR (23% vs 21%). After 6 cycles, 47% pts in the KRd arm and 29% in the R arm achieved MRD-negativity (p=0.017). 34 KRd pts eligible for de-escalation converted to R alone after C8 and were analyzed on the KRd arm per intention-to-treat. At median follow-up of 33.8 mo, 23 pts (25%) on the KRd arm and 38 pts (44%) on the R arm progressed; estimated median PFS was 59.0 mo for KRd vs 41.4 mo for R (Hazard Ratio 0.56, logrank p=0.026). At cutoff, 90% of KRd and 87% of R pts were alive; no deaths were treatment-related. All-grade toxicities were generally comparable between arms. The most common grade 3+ AEs and those of special interest were neutropenia (KRd 47%; R 59%), thrombocytopenia (KRd 13%; R 7%), infections (KRd 15%; R 6%), cardiovascular toxicities (KRd 4%, R 5%), and secondary malignancies (KRd 2, R 2). Image:Summary/Conclusion: This is the first randomized phase 3 trial demonstrating superior PFS with extended post-transplant KRd therapy compared to R maintenance. Therefore, MRD/risk-adapted post-ASCT extended KRd treatment may represent a new standard of care.

PB1982: DEEPENING OF RESPONSE IN PATIENTS WITH MULTIPLE MYELOMA AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION: A MULTICENTRIC STUDY IN A LATINO POPULATION

Background: Over the last decades Multiple myeloma (MM) outcomes have shown a continuous improvement as novel drugs and maintenance therapy have been incorporated. However, availability of these resources is still limited in low- and middle-income countries (LMIC), where autologous stem cell transplant (ASCT) continues to be the best strategy to achieve better response and survival. Aims: Our aim was to analyze the deepening of response after ASCT and its impact over survival outcomes in newly diagnosed MM (NDMM) patients. Methods: Multicenter retrospective study that included patients ≥ 18 years of age with NDMM who received upfront ASCT as consolidation between 2015 and 2020 at six transplant centers in Mexico. Response after ASCT was defined as any improvement of response according to IMWG criteria. Novel agents were considered: proteasome inhibitors, immunomodulatory drugs, other than thalidomide, and monoclonal antibodies. Results: A total of 126 patients were included. The median age at diagnosis was 53.1 years (range 38-68) and 55% were male. Most common isotype was IgG (60.3%) and extramedullary disease was present in 12.2%. Regarding risk, 72.7% were classified as ISS ≥2 and 18.7% of patients evaluated had high-risk cytogenetics (n=64). Induction therapy with novel agents was administered to 77 patients (61.2%). Pre-ASCT, 73.1% had a very good partial response (VGPR) or better. Conditioning regimen was melphalan-based in 96%, with 15.9% being oral melphalan. Five patients received a tandem ASCT (4.0%) and 86 (68.3%) maintenance therapy, being thalidomide-based in 54.6%. Response after ASCT was evaluated in 86.5% (n=109), with an improvement of response in 27.5%. Patients with ≥VGPR were 82.5%. The median overall survival (OS) of the cohort was 119 months (90.0 – 149.34) and progression-free survival (PFS) was 67.1 months (61.3 - 72.8). Deepening and maintenance of response after ASCT were associated with a better OS, 119.7 vs. 63.0 months (p=0.017) (Figure 1). Image:Summary/Conclusion: This is the first multicenter study of a Latino population that reports the impact of transplant on response deepening and survival of NDMM patients. ASCT improved responses in almost 30% of our patients, being this related to an increased OS. It is of utmost importance to increase access to novel drugs in low- and middle-income countries, albeit ASCT continues to be the standard of care in patients with NDMM and demonstrated to be the best consolidation strategy to improve response and survival in our population and therefore its use should be promoted and expanded in LMIC.

P888: REPLACING STEROIDS IN TRANSPLANT-INELIGIBLE MULTIPLE MYELOMA: THE PHASE 2 ISATUXIMAB-BORTEZOMIB-LENALIDOMIDE-DEXAMETHASONE REST STUDY

Background: Standard therapies for newly diagnosed multiple myeloma (NDMM) patient’s ineligible for autologous stem-cell transplantation (ASCT) have been lenalidomide-dexamethasone (Rd), bortezomib-lenalidomide-dexamethasone (VRd) or bortezomib-melphalan-prednisone (VMP). The benefit of adding an anti-CD 38 monoclonal antibody (mAb) to the standard treatments of VMP and Rd has been demonstrated in two large phase 3 studies (Facon, 2019. Mateos, 2018). Isatuximab is an anti-CD38 mAb approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone to treat relapsed/refractory MM, and has also shown clinical responses as combination therapy to treat NDMM (Trudel, 2019). Corticosteroids have been the backbone of most myeloma targeted therapies since the discovery of their effectiveness. Due to the continuous treatment paradigm, the cumulative dose of corticosteroids in patients is substantial. Steroids inflict reduction in both short- and long-term quality of life and increase patients’ receptiveness for infections. Infections are one of the main reasons for complications and death during active first line treatment, and the rate rises with age. Both steroid-free regimens and regimens with reduced corticosteroids have demonstrated improved safety and similar efficacy as regimens containing steroids. Aims: The study will evaluate isatuximab (Isa) in combination with bortezomib (V) and lenalidomide (R) with minimal dexamethasone (d) as first-line treatment in transplant-ineligible patients. The primary endpoint is the number of patients who achieve measurable residual disease negative (Euroflow NGF 10-5) complete response during and/or after 18 cycles of study treatment. Secondary endpoints include progression free survival, overall survival, overall response rate (ORR), safety evaluations and patient-reported outcome. Methods: The REST study is an academic, single arm, open-label, phase 2 study of NDMM patients ineligible for ASCT. 50 patients will be included and receive Isa-VRd (Isa:10 mg/kg IV Days 1, 8, 15, 22 during cycle 1, QW cycle 2-18; V: 1,3 mg/m2 SC Days 1,8,15 during cycle 1-8; R: 25 mg PO Days 1-21 during all cycles; d: 20 mg PO Days 1,8,15,22 only for the first 2 cycles), all 28-day cycles. Results: As of January 31, 2022, 17 patients have been enrolled. Baseline characteristics can be found in Table 1. At data-cutoff, the median number of cycles started by patients was 3.6 (range 1-8) and the median duration of exposure was 16 (range 3-28) weeks. 8 patients developed 14 grade ≥3 non-hematological adverse eventd (AE), including infections (n=7), fever (n=1), skeletal pain (n=2), acute renal failure (n=1), peripheral sensory neuropathy (n=1), diarrhea (n=1) edema (n=1). There were no AEs leading to definitive treatment discontinuation. At a follow up of 6 months, the ORR was 100% (15/15) and the ≥very good partial response rate was 53.3% (8/15 patients). Image:Summary/Conclusion: Isa-VRd in the transplant ineligible population has a tolerable safety profile. Isa-VRd is showing encouraging preliminary efficacy in NDMM ineligible for transplant. Enrollment and follow-up is ongoing. Acknowledgements: Sanofi sponsors the REST study.

PB2038: LENALIDOMIDE OR BORTEZOMIB AS MAINTENANCE TREATMENT OVERCOMES INFERIOR IMPACT OF HIGH-RISK CYTOGENETIC ABNORMALITIES IN TRANSPLANT-INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA IN CHINA

Background: Maintenance (MT) after front-line therapy is recommended in guidelines for multiple myeloma. However, no adequate data has shown the current situation of MT in China yet, especially in transplant-ineligible patients with newly diagnosed MM (NDMM). Aims: We conducted this retrospective real-world study on efficacy and safety of the mainstream maintenance regimens in non-transplant NDMM patients—lenalidomide (L-MT), bortezomib (B-MT) and thalidomide (T-MT). Methods: Clinical data were collected from 11 centers of North China MM Registry from January 2010 to July 2021. Patients achieving partial remission (PR) or better after induction therapy were included. The progression-free (PFS) and overall survival (OS) from MT, and drug toxicities were compared in L-MT, B-MT and T-MT groups. Thalidomide 75-150mg/day was administrated in T-MT group. L-MT group received lenalidomide as 25mg every other day or 10mg daily, on days 1–21 in a 28-day cycle. Bortezomib (1.3 mg/m2 s.c.) was administered every 2 weeks or 4 vials every 3 months. Dexamethasone was given along with T, L or B in some patients. Results: A total of 350 patients were enrolled including 155 in T-MT, 141 in L-MT and 54 in B-MT. At baseline, the gender ratio, paraprotein isotype, ISS and R-ISS stage were comparable. Patients on L-MT were significantly older than the other groups. Meanwhile, greater proportions of patients in L-MT and B-MT group had high-risk cytogenetic abnormalities (HRCA), defined as amplification 1q21, deletion 17p, t(4,14), t(14,16). The median follow-up duration since maintenance was 42.5, 22.0 and 26.4 months (m) in T-MT, L-MT and B-MT groups, respectively. Disease progression was recorded in 101 patients (65.2%) with T-MT, 58 (41.1%) with L-MT and 22(40.7%) with B-MT. While mortality was 51(32.9%), 23(16.3%) and 5(9.3%), respectively. The median PFS was 23.7m in T-MT, as compared with 27.4m in L-MT and 29.7m in B-MT (p=0.52). Median OS was 90.7m in T-MT, whereas not reached (NR) in L-MT and B-MT groups (p=0.46). Patients achieving complete response (CR) or stringent CR (sCR) before MT had prolonged PFS compared to those with VGPR or less in T-MT (40.1m vs 17.2m, p＜0.01), while comparable in L-MT (27.4m vs 26.9m, p=0.09) or B-MT group (NR vs 29.7m, p=0.34). Meanwhile, patients in each group had similar OS despite of different response before MT, their PFS and OS were also comparable despite of different induction regimens. Long-term duration of maintenance which was defined as over 24 months translated into significant better PFS in all groups (T-MT 57.2m vs 12.1m, L-MT 54.3m vs 19.2m, B-MT 37.3m vs 16.7m, p＜0.01), as well as better OS. For patients with high-risk cytogenetic abnormalities, T-MT resulted in impaired PFS (12.2m vs 21.2m, p=0.04) and OS (54.9m vs NR, p＜0.01). In contrast, PFS and OS were both comparable in patients with L-MT or B-MT no matter with HRCA or not. The main reason of maintenance withdrawal was disease progression. Adverse event related discontinuation was seen in 8.5%, 5.1% and 8.3% of the patients in T-MT, L-MT and B-MT, respectively. Image:Summary/Conclusion: In this multi-centered real-world maintenance study, thalidomide, lenalidomide or bortezomib after front-line therapy in non-transplant patients with NDMM has similar PFS and OS. However, patients on L-MT and B-MT have greater proportion of HRCAs, which drags down survival in T-MT, while L-MT and B-MT reverses the negative effect. Clinicians in the real practice prefer to select lenalidomide or bortezomib as maintenance in patients with HRCAs, while thalidomide is still an option for patients with standard risk.

Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for multiple myeloma: final results of the LYRA study

In the primary analysis of LYRA, daratumumab + cyclophosphamide/bortezomib/dexamethasone (DARA + CyBorD) was effective and well tolerated in newly diagnosed multiple myeloma (NDMM) and relapsed multiple myeloma (RMM). We report the final analysis of LYRA (median months of follow-up: NDMM, 35.7; RMM, 35.3) after all patients completed study therapy, were followed for 36 months, or discontinued. Patients received DARA + CyBorD induction, autologous stem cell transplant (if eligible), and 12 months of daratumumab maintenance. Eighty-seven NDMM patients enrolled, 39 underwent transplant, and 63 completed maintenance. Rates of complete response or better were 48.7% and 29.8% for NDMM transplant and NDMM non-transplant patients, respectively, and 36-month progression-free survival rates were 69.3% and 72.6%. Grade 3/4 treatment-emergent adverse events occurred in 61.6% of NDMM patients. Efficacy and safety data are also reported for the smaller RMM cohort (n = 14). DARA + CyBorD followed by daratumumab maintenance was well tolerated and achieved deep, durable responses in NDMM and RMM.

Circulating tumor DNA analysis and association with relapse in patients with primary refractory multiple myeloma receiving secondary salvage therapy.

8037 Background: Multiple myeloma (MM) is an incurable plasma cell malignancy with a 5 year-median overall survival (OS) in newly diagnosed (ND) patients. Real-world data reveals that 23% of transplant eligible (TE) ND MM patients relapse within 12 months of starting first-line bortezomib (1LB) based therapy and of these ̃50% will fail secondary therapy and die within 18 months. It is currently impossible to identify these high-risk patients and genomic studies could potentially inform alternative secondary therapeutic options. We propose that circulating tumour DNA (ctDNA) analysis could provide a more holistic approach to determine genomics of high-risk patients than bone marrow (BM) tumour DNA analysis in this genetically heterogenous multi-site malignancy. Methods: Peripheral blood plasma and BM samples (n = 186) were obtained at baseline, cycle 3 day 1 (C3D1), end of the study (EOS) and/or relapse, whichever appeared earlier, from a Phase II multicentre single arm study of carfilzomib-thalidomide-dexamethasone (KTd) in 50 TE ND MM patients who were refractory or registered suboptimal response to 1LB (Australasian Leukaemia and Lymphoma Group - MM17 trial). Somatic variants were identified in BM or ctDNA with ultra-sensitive targeted amplicon sequencing of 22-genes known to be mutated in MM. Mutational spectrum was correlated to standard MM risk factors including International Staging System (ISS), response to 1LB and KTd, cytogenetics/FISH, lactate dehydrogenase (LDH) levels, progression-free survival (PFS) and OS. Results: Our initial analysis of ctDNA mutational proportions between patients who did not or did experience relapse on KTd revealed a significantly higher proportion of RAS/RAF (3% vs 25%), or ATM/ATR/TP53 (17% vs 41%; p &lt; 0.0001), respectively, in relapse patients. Subsequently, we correlated ctDNA RAS/RAF and/or ATM/ATR/TP53 mutational presence to standard MM risk factors. We identified a shorter PFS and OS for ISS Stage 2 and 3 compared to Stage 1 patients (p = 0.002 and p = 0.02, respectively) and a significantly higher proportion of RAS/RAF or ATM/ATR/TP53 mutations in patients with refractory as compared to sub-optimal response to 1LB therapy (p = 0.0002). Patients with RAS/RAF or ATM/ATR/TP53 mutations in ctDNA at the time of starting salvage therapy also had a shorter PFS and OS on KTd (p = 0.003 and p = 0.02, respectively). Sequential ctDNA analysis discovered that in 87.5% of patients, one or more of the dominant mutations present at the time of relapse were already present at the start of salvage therapy. Conclusions: Our analysis reveals that RAS/RAF and ATM/ATR/TP53 mutations in ctDNA could be prognostic biomarkers of response to secondary salvage therapy in primary refractory patients thus providing the opportunity to design targeted salvage treatment paradigms in high-risk MM patients.

Bortezomib, epirubicin, and dexamethasone (PAD) results in superior free-progression survival compared to bortezomib, cyclophosphamide, and dexamethasone (VCD) treatment in non-transplantation newly diagnosed multiple myeloma patients aged between 50 to 65: a retrospective single-center analysis in non-transplant patients

BackgroundTo explore the optimum induction therapy for patients with newly diagnosed multiple myeloma (NDMM) who are eligible but have not yet received autologous stem cell transplantation (ASCT) in China.MethodsA total of 140 NDMM patients with cytogenetic background were selected from the Chang Zheng Hospital for this study. The induction therapy consisted of combined bortezomib (1.3 mg/m2, i.v.), cyclophosphamide (200 mg, i.v.), and dexamethasone (20 mg, i.v.) (VCD); or combined bortezomib (1.3 mg/m2, i.v.), epirubicin (50 mg/m2, i.v.), and dexamethasone (20 mg, i.v.) (PAD). All patients received 4–6 cycles of induction therapy until the first remission (defined as reaching at least partial remission), followed by thalidomide (100 mg/every night, p.o.) as the maintenance therapy. Data was analyzed using SPSS18.0 software and Kaplan-Meier and Cox regression analyses.ResultsOf the 140 patients enrolled, 56 were treated with VCD and 84 received the PAD regimen. Compared to patients treated with VCD, patients receiving PAD treatment showed better free-progression survival (PFS) (hazard ratio: 0.355; 95% confidence interval: 0.214 to 0.591; P<0.001) and response rates, defined as achieving very good partial response (VGPR) or better (VCD vs. PAD: 47/56 or 83.9% vs. 77/84 or 92.8%; P=0.087). Similarly, the superior efficiency of PAD treatment was observed in different cytogenetic abnormality subgroups, even in patients with 1q21 amplification.ConclusionsThis analysis demonstrated that PAD treatment resulted in better PFS compared to VCD in NDMM patients (aged 50–55 years old) who are eligible for but refuse ASCT therapy.

Sequential EHR-based dynamic graph network for multiple myeloma detection and feature interaction investigation.

e13591 Background: Electronic Health Records (EHR) provide the possibility of leveraging modern machine learning algorithms for disease detection prediction. Since a patient’s medical journey contains a complex pattern and it is difficult to identify interactive feature impacts, we propose to reconstruct patients’ attributes at different time points into dynamic graphs. Then we can use graph-based learning algorithms to enhance the predictive precision and identify leading feature interactions that reveal key services transitions. Methods: Sequential EHR like diagnosis (Dx), procedure (Px) and prescription (Rx) can be transformed into dynamic temporal graphs with nodes representing attributes, services, and medical status and edges representing patient-object interactions. Also, graph based sequential recommendation can use structured historical behavior trajectories as input, aiming to predict patient’s next behavior. Then, the model can investigate patients’ time-sensitive features interactively identifying a potential disease and then output a probability of getting that disease. Dynamic graphs can also help to track patient’s medical treatment/drug use service transitions. Results: We applied our method on a Newly Diagnosed Multiple Myeloma (NDMM) dataset consisting of 1.5 million candidates’ longitudinal medical claims from 2017 to 2020 with diagnosis rate around 0.6%. In this data set, patients’159 aggregated Dx, Rx and Px features, together with 30 demographic attributes are updated monthly. The model was trained on 4 monthly data cohorts from the 12/2017 to 03/2019 period and its performance was tested on 9 monthly cohorts from year 2020. The 1000 patients scored as having highest risk were evaluated for the predictive precision which was around 6.5% This precision compares most favorably relative to the reported 0.76% lifetime risk of getting multiple myeloma in US. We also captured the top, service transitions in NDMM patients having 30% more frequency than those in overall populations. Conclusions: The novel dynamic graph-based learning approach on a large-scale EHR dataset demonstrates the advancement of the disease detection methodology. While the outcome of this model significantly improves the accuracy of predictive precision, it also helps identify more meaningful key drivers attributing to disease. The incremental new patients identified through this novel model will provide a better basis for the evolving identification solution within Biopharma industry.

Incidence and risk factors for bacterial infection in newly diagnosed multiple myeloma patients undergoing treatment with bortezomib, lenalidomide, and dexamethasone (RVD).

e20008 Background: Infection is an important cause of morbidity and mortality in newly diagnosed multiple myeloma (NDMM), but the risk of infection using novel treatment regimens is incompletely described in the literature. There are mixed trial results for antibacterial prophylaxis to reduce infection risk in newly diagnosed multiple myeloma and its use remains controversial. Methods: To evaluate the incidence of bacterial infection and early mortality in patients receiving bortezomib, lenalidomide, and dexamethasone (RVD) for NDMM, we performed a retrospective single-center cohort study of patients treated between 01/2014-01/2020. Demographic and clinical data were collected. Two cohorts were generated for those patients with or without bacterial infection during the follow-up period. A multivariate logistic regression was utilized to determine risk factors for bacterial infection. Variables with a P-value &lt;0.2 on univariate analysis were considered for the model. For co-linear variables with a P-value &lt;0.2 on univariate analysis, only one variable was included in the multivariable model. A receiver operating characteristic (ROC) curve was generated to assess the sensitivity and specificity of the model. Results: Of 144 patients, 21 patients (14.5%) experienced a bacterial infection of any grade. 11% of patients received pneumocystis prophylaxis, and 1 patient received levofloxacin prophylaxis. 11 (7.6%) patients experienced grade 3 (G3) or higher infection. One patient died in our cohort; there were no deaths from infection. G3 neutropenia occurred in 11% of patients with 2% experiencing any grade febrile neutropenia. Pneumonia and urinary tract infections were common, affecting 8(5.5%) and 6 (4.2%) patients, respectively. On multivariable analysis (Table), age, smoking history, history of diabetes, antibiotic use in the 60 days preceding 1st cycle of RVD, and high-risk cytogenetics (HR CG) were associated with a greater likelihood of experiencing a bacterial infection. The area under the ROC curve of the multivariable model was 0.829 (95% CI 0.729-0.934). Conclusions: The overall incidence of bacterial infection in NDMM patients receiving induction with RVD was low despite minimal use of antibacterial prophylaxis. Early mortality was uncommon and not attributable to infection. Clinical features may identify a subgroup of patients at greater risk of infection during induction therapy for MM and may impact clinical decisions to utilize antibacterial prophylaxis.[Table: see text]

ATLAS: A phase 3 randomized trial of carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma.

8001 Background: Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), suggesting a benefit of post-ASCT KRd therapy. Here we directly compare that strategy to standard lenalidomide (R) maintenance. Methods: This international open-label phase 3 randomized trial recruited newly-diagnosed MM patients (pts) who received any induction therapy for up to 12 months (mo) followed by single ASCT and achievement of at least stable disease within 100 days afterward. Pts were randomized to receive either KRd or R, stratified by post-transplant response (≥VGPR vs &lt; VGPR) and cytogenetic risk [standard risk (SR) vs high [HR: presence of t(4;14), t(14;16), or del(17p)]. Pts randomized to KRd received carfilzomib 36 mg/m2 on days (D) 1,2,8,9,15,16 for 4 cycles (C) then D1,2,15,16 starting C5; R 25 mg D1-21, and dexamethasone 20 mg D1,8,15,22 in 28-day cycles. KRd pts with SR who reached IMWG-defined MRD-negativity after C6 de-escalated therapy to R alone after C8 (KRd- &gt; R); the rest continued KRd through C36 followed by R alone until progression. Pts randomized to R received lenalidomide 10 mg C1-3 and then 15 mg daily. The primary objective was to compare progression free survival (PFS) rate between the two arms. Based on historical PFS rates, a sample size of 180 Pts was calculated to provide 85% power with 2-sided alpha 0.05. Results: 180 pts were enrolled (R n = 87; KRd n = 93) through 10/21/20; data cutoff was 12/31/21. Pt characteristics in the KRd and R arms were balanced for median age (58 vs 59 yrs), &gt;VGPR (88% vs 92%), and HR (23% vs 21%). After 6 cycles, 47% pts in the KRd arm and 29% in the R arm achieved MRD-negativity (p = 0.017). 34 KRd pts eligible for de-escalation converted to R alone after C8 and were analyzed on the KRd arm per intention-to-treat. At median follow-up of 33.8 mo, 23 pts (25%) on the KRd arm and 38 pts (44%) on the R arm progressed; estimated median PFS was 59.0 mo for KRd vs 41.4 mo for R (Hazard Ratio 0.56, logrank p = 0.026). At cutoff, 90% of KRd and 87% of R pts were alive; no deaths were treatment-related. All-grade toxicities were generally comparable between arms. The most common grade 3+ AEs and those of special interest were neutropenia (KRd 47%; R 59%), thrombocytopenia (KRd 13%; R 7%), infections (KRd 15%; R 6%), cardiovascular toxicities (KRd 4%, R 5%), and secondary malignancies (KRd 2, R 2). Conclusions: This is the first randomized phase 3 trial demonstrating superior PFS with extended post-transplant KRd therapy compared to R maintenance. Therefore, MRD/risk-adapted post-ASCT extended KRd treatment may represent a new standard of care. Clinical trial information: NCT02659293.

The impact of complex karyotype identified by conventional cytogenetics on survival outcomes of 1,000 patients with newly diagnosed myeloma (NDMM).

8063 Background: Complex karyotype (CK), defined as two or more cytogenetic abnormalities on conventional metaphase cytogenetics, is not routinely used for the risk-stratification or treatment determination in patients with newly diagnosed myeloma (NDMM). Here, we present a retrospective analysis utilizing our institutional data of NDMM patients treated with RVD and a risk-adapted maintenance strategy at the Winship Cancer Institute of Emory University to assess the impact of CK on long-term outcomes. Methods:1000 consecutive NDMM patients treated with RVD induction therapy (R25mg/day, days 1-14; V1.3 mg/m2, days 1,4,8,11 and D40mg once/twice weekly as tolerated) were identified from January 2007 to August 2016. Demographics, clinical characteristics and outcome data for patients were obtained from our institutional review board-approved myeloma database. Responses were evaluated per IMWG Uniform Response Criteria. Results: The median age of this cohort was 61 (range 16-83). Notable patient characteristics include: M/F 54.6%/45.4%, W/AA 61.8%/35.9%; ISS I/II/III 45.8%/30.8%/23.4%. R-ISS I/II/III 39.9%/48.7%/11.5%; Isotype IgG/IgA/FLC 59.2%/19.0%/15.7%; standard risk(SR)/high risk(HR) 71.2%/15.8%. ISS data was available for 75% of patients; R-ISS was available for 41% of patients. HR disease defined as the presence of t(4;14), t(14;16), del(17p) and/or CK. Frequency of specific CTG abnormalities were:14.9% with +1q21, 8.3% with del(1p),12.1% with t(11;14), 25.7% with del(13), 13.9% with CK, 2.8% with t(14;16), 10% with del(17p), and 4.8% with t(4;14). 11.9% of patients were classified high risk by FISH alone, 10.0% of patients were classified as high risk by complex karyotype(CK), and 3.9% of patients were classified as high risk by the presence of both high-risk FISH and CK. With a median follow up of 88.4 months, the median PFS (mPFS) for patients HR by FISH alone was 47.6 months (95% CI 35.2-59.9), for HR by CK alone was 46.9 months (95% CI 28.1-65.7) and for HR by both was 24.0 months (95% CI 8.3-39.7). The mOS for HR by FISH alone was 94.7 months (95% CI 74.4-115.1),HR by CK alone was 105.9 months (95% CI 60.8-151.0) and HR by both was 41.0 months (95% CI 24.2-57.8). Conclusions: CK by conventional metaphase cytogenetics is not currently included in the risk-stratification or risk stratification models of NDMM patients. In patients with a complex karyotype at time of diagnosis, mPFS and mOS is essentially the same as patients classified HR by FISH abnormalities. When compared to SR patients, prognosis is significantly worse, therefore the standard treatment approach is likely insufficient. As many centers do not routinely perform chromosome analysis, this highlights a gap in providing appropriate risk-stratified care. Moreover, NDMM with HR features by FISH and CK portends a poor prognosis for which alternative treatment strategies may need to be explored.

Updated survival with extended follow-up on patients with newly diagnosed multiple myeloma treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy and a risk-stratified maintenance approach.

8061 Background: Lenalidomide, bortezomib, and dexamethasone (RVD) has been established as an effective and well-tolerated induction regimen in patients with newly diagnosed myeloma (NDMM). We have previously published a retrospective analysis of 1000 patients treated with RVD and risk-stratified maintenance therapy showing a median PFS of 65 months and median OS of 126 months for the entire cohort (Joseph et al, JCO 2020). This data has served as an important benchmark for evaluating upfront treatment strategies in NDMM. Here, we present updated survival data with extended follow up on this patient population treated at the Winship Cancer Institute of Emory University. Methods: From January 2007 to August 2016, 1000 consecutive newly diagnosed myeloma patients treated with RVD induction therapy (R-25 mg/day on days 1-14, V-1.3 mg/m2 on days 1,4,8,11 and D-40 mg once/twice weekly as tolerated) were identified. Demographics, clinical characteristics, and outcomes data for the patients were obtained from our institutional review board-approved myeloma database. Responses were evaluated per IMWG Uniform Response Criteria. Results: The median age of this cohort was 61 (range 16-83). Other notable patient characteristics include: M/F 54.6%/45.4%, W/AA 61.8%/35.9%; ISS I/II/III 45.8%/30.8%/23.4%. R-ISS I/II/III 39.9%/48.7%/11.5%; Isotype IgG/IgA/FLC 59.2%/19.0%/15.7%; standard risk(SR)/high risk (HR) 71.2%/15.8%.. High risk disease was defined as the presence of t(4;14), t(14;16), del(17p), and/or complex karyotype by conventional metaphase cytogenetics. 81.8% of patients underwent ASCT, with 16.8% having deferred ASCT. 75.3% of patients were initiated on maintenance therapy. With a median follow up of 88.4 months, the median PFS for the entire cohort was 68.7 months (95% CI 61.8-75.5) and the median OS was 128.9 months. The median PFS for HR patients was 42.4 months (95% CI 35.7-48.9), and the median PFS for SR patients was 80.3 months (95% CI 72.8-87.8). The median OS for SR patients was not reached, and for HR patients was 86.6 months (95% CI 70.1-103.1). Conclusions: Updated analysis with long-term follow up of this database of 1000 NDMM patients treated with RVD continues to demonstrate that, in combination with a risk-stratified maintenance strategy, RVD delivers durable remissions and impressive long-term outcomes. This study remains the largest cohort of patients treated with RVD reported to date, and continues to show the efficacy of this upfront treatment approach in newly diagnosed myeloma.

Establishment of a prediction model for disease progression within one year in newly diagnosed multiple myeloma patients

ABSTRACT Purpose Multiple myeloma is still an incurable disease In the past decade, with the continuous progress of treatment methods, the progression-free survival of patients has been prolonged, but some patients still progress in the early stage of the disease. Our research analyses the clinical laboratory indicators of newly diagnosed multiple myeloma (NDMM) patients, to obtain the relevant factors of disease progression within one year in MM patients and to establish a prediction model. Methods: 108 MM patients treated in our hospital from January 2015 to January 2020 were retrospectively analyzed. After univariate and multivariate logistic regression analyses, the related factors of disease progression within one year in NDMM patients were obtained, and a prediction model was established. Results: Treatment regimen containing at least two targeted drugs (OR = 0.226, 95% CI 0.068-0.753), increased lactate dehydrogenase(LDH, OR = 3.452, 95% CI 1.101-10.826) and increased serum corrected calcium(OR = 4.466, 95% CI 1.346-14.811) were identified as potential predictors by statistical analysis. The prediction model was obtained: x = −2.042-1.489 × treatment regimen (including at least two targeted drug assignment as 1, otherwise 0) + 1.239 ×LDH (U/L, lactate dehydrogenase elevation assignment as 1, normal as 0) +1.496 × serum corrected calcium (mmol/L, serum corrected calcium elevation assignment as 1, normal as 0). Receiver operating characteristic curve analysis showed that the model has good predictive performance. Conclusion: The possibility of disease progression within one year can be predicted by the prediction model. The model can be used as a reference for clinicians to make individualized treatment plans for patients so that patients can obtain better treatment effects.

Prognostic Significance of the Stage at Which an MRD-Negative Status Is Achieved for Patients With Multiple Myeloma Who Received ASCT.

ObjectiveTo explore the prognostic significance of the stage at which a minimal residual disease (MRD)-negative status is achieved for patients with newly diagnosed multiple myeloma (NDMM) who received autologous hematopoietic stem cell transplantation (ASCT).Cases and MethodsA retrospective analysis of 186 NDMM patients who received “induction therapy-ASCT-maintenance therapy” in our center and achieved an MRD-negative status was performed. Patients were divided into three groups, A (induction therapy), B (3 months after ASCT), and C (maintenance therapy), according to the stage at which an MRD-negative status was achieved.ResultsThe median time to progression (TTP) of 186 patients was not reached; the median overall survival (OS) was 113.8 months. The median TTP of the patients in three groups was not reached (P=0.013), and the median OS of the patients in three groups was not reached, not reached, and 71.2 months, respectively (P=0.026). Among patients with standard-risk cytogenetics, the median TTP of those in all three groups was not reached (P=0.121), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.091). Among patients with high-risk cytogenetics, the median TTP of those in three groups was not reached, 53.9 months, and 35.8 months (P=0.060), and the median OS was not reached, 71.2 months, and 60.2 months, respectively (P=0.625). Among patients with R-ISS stage I-II, the median TTP of those in three groups was not reached (P=0.174), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.186). Among the 29 patients with R-ISS stage III, the median TTP of those in the 3 groups were unreached, unreached, and 35.1 months (P<0.001), and the median OS was unreached, unreached, and 48.5 months, respectively (P=0.020). In all enrolled patients, the stage of reaching MRD-negative was an independent prognostic factor for TTP, rather than a prognostic factor for OS. The stage of reaching MRD-negative in patients with R-ISS III was an independent prognostic factor for OS.ConclusionFor the same patients who are MRD-negative, the prognoses of those who achieve an MRD-negative status at different groups are different. The stage at which an MRD-negative status is achieved can predict the prognosis of patients with R-ISS stage III.

Improvement in Post-Autologous Stem Cell Transplant Survival of Multiple Myeloma Patients: A Long-Term Institutional Experience.

Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression-free survival (PFS) and overall survival (OS). We performed a retrospective survival analysis on newly diagnosed MM (NDMM) patients receiving ASCT from 1992-2016 at the Ohio State University. A total of 1001 consecutive NDMM patients were eligible. Patients were split into five groups based on historic changes in novel agents for the treatment of MM. Across the years (1992-2016), there was a statistically significant improvement in both PFS (p &lt; 0.01) and OS (p &lt; 0.01). Significant improvements in both PFS and OS were seen in patients ≤65 years (p &lt; 0.001 and p = 0.002) and &gt;65 years old (p &lt; 0.001 and p = 0.001), respectively. Improved PFS and OS were seen in both standard-risk (p &lt; 0.001 and p &lt; 0.001) and high-risk patients (p &lt; 0.001 and p = 0.019). The post-transplant response showed statistically significant improvement across the years (p &lt; 0.01). Survival rates for NDMM patients have significantly improved primarily due to the inclusion of novel therapies and post-ASCT maintenance.

A single-center retrospective analysis of 100 consecutive cases treated with lenalidomide/bortezomib/dexamethasone in newly diagnosed multiple myeloma

Objective: To investigate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (RVD) in patients with newly diagnosed multiple myeloma (NDMM). Methods: A total of 100 consecutive NDMM patients treated with RVD from August 2016 to September 2020 at Peking University People's Hospital were retrospectively analyzed, including response, drug toxicity, follow-up and survival, and subgroup analysis. Results: The median follow-up time was 19.5 (2.0-57.0) months. For patients undergoing autologous stem cell transplantation (ASCT) after RVD regimen, the objective response rate (ORR)/complete response+stringent complete response (CR+sCR)/≥very good partial response (VGPR) rates were 100%, 73.3% (33/45), 95.6% (43/45) respectively. For 54 patients not receiving transplantation, the ORR/CR+sCR/≥VGPR rates were 79.6% (43/54), 18.5% (10/54), 51.9% (28/54) respectively. As to the survival analysis, 2-year progression free survival (PFS) rates were 84.5% and 70.9% in transplant and non-transplant patients respectively (P=0.102). Two-year overall survival (OS) rates were 100% and 80.8% in transplant and non-transplant patients respectively (P=0.003). The common hematologic adverse events (AEs) were thrombocytopenia (33%) and neutropenia (25%). Abnormal liver function (43%) and peripheral neuropathy (24%) were recognized more as non-hematologic AEs. Conclusion: RVD as front-line regimen has high efficient response rate and acceptable safety in Chinese NDMM patients.