Efficacy Of Lenalidomide Research Articles

Carfilzomib and Lenalidomide for the Treatment of Primary Plasma Cell Leukemia: Final Results of the Prospective Phase 2 EMN12/HOVON-129 Study for Patients Aged ≥66 Years

Introduction. Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell disorder with a very poor prognosis, requiring urgent action to prevent early mortality and to control the disease and complications. The EMN12/HOVON-129 study assessed the efficacy of carfilzomib and lenalidomide as part of first-line therapy in pPCL. The trial enrolled patients (pts) aged 18 years and older, with different treatment for those 18-65 and ≥66 years. Here we report the results for pts in the age-group ≥66 years. Methods. The EMN12/HOVON-129 study is a prospective, non-randomized, phase 2, multicenter study for previously untreated pPCL pts. Inclusion criteria were newly diagnosed pPCL (in this study defined as >2x109/L circulating monoclonal plasma cells and/or plasmacytosis >20% of the differential white cell count) and WHO performance status 0-3. Main exclusion criteria were severe cardiac or pulmonary dysfunction and creatinine clearance <15 ml/min. There were no restrictions based on blood counts. Pts ≥66 years received induction therapy with eight 28-day cycles of carfilzomib-lenalidomide-dexamethasone (KRd; carfilzomib 20/36 mg/m2 on days 1,2,8,9,15,16; lenalidomide 25 mg on days 1-21; dexamethasone 20 mg on days 1,2,8,9,15,16,22,23), followed by maintenance with carfilzomib (27 mg/m2 on days 1,2,15,16 for the first twelve cycles; then 56 mg/m2 on days 1,15) and lenalidomide (10 mg on days 1-21/28 days) until progression. The primary endpoint was progression-free survival (PFS); secondary endpoints were response rate, overall survival (OS), and toxicity. Results. From October 2015 to August 2021, we enrolled 61 pts with pPCL: 36 aged ≤65 years and 25 aged ≥66 years. Among the 25 pts aged ≥66 years, median age was 71 years (range 66-84); 68% had bone disease; and WHO performance status was 2 in 24% and 3 in 16% of pts. Median plasma cell percentage in bone marrow biopsy was 80% (10-100). Median peripheral blood plasma cell count was 3.8x109/L (range 2.0-52); median platelet count was 142x109/L (range 13-384); and median GFR was 56 ml/min (range 24-95). Most of pts had high-risk disease features, as proved by elevated LDH in 52% and high frequency of poor-risk genetic lesions (del(17p) in 20%, t(4;14) in 4%, t(14;16) in 4%, and gain/amp(1q) in 48%). In addition, 12% of pts had extramedullary plasmacytomas. ISS stage III was present in 68% and Revised ISS stage III in 40%. At the data cut-off (July 1, 2022), among the 25 pts, 17 (68%) received the planned 8 cycles of induction treatment, achieving ≥partial response (PR) in 80%, ≥very good (VG)PR in 68%, and ≥complete response (CR) in 32% of pts. Sixteen pts (64%) received maintenance treatment. Best response on protocol was ≥PR in 80%, ≥VGPR in 68% and ≥CR in 36%; 3 out of 4 pts in CR who could be evaluated for minimal residual disease (MRD) achieved MRD negativity (10-5) by flow cytometry. With a median follow-up of 24.6 months (range 7.9-59.6), the median PFS was 13.8 months (95% CI 9.2-35.5), which was sufficient to reject our null hypothesis (median PFS=6.5 months). With 16 pts having died (8 due to disease progression, 2 unknown, 1 pneumonia, 1 sepsis, 1 systemic aspergillus infection, 1 small intestinal SPM, 1 disseminated intravascular coagulation, 1 respiratory failure due to COPD exacerbation), median OS was 24.8 months (95% CI 14-not reached [NR]; Figure). Adverse events mainly occurred during the first two cycles of KRd and decreased thereafter. Overall, 36% of pts had grade (G)3 and another 36% G4 adverse events. G3 and G4 hematologic toxicity rates were 8% and 12%, respectively. Infections (20% and 16%) and respiratory events (16% and 4%) were the most common G3 and G4 non-hematologic toxicities. Twenty-two pts (88%) discontinued protocol treatment, mainly because of progression (13 pts, 59%). Conclusions. KRd is a potent treatment strategy to control disease in pPCL pts over 65 years of age, with not negligible, but generally manageable, treatment-related toxicities. Of note, along with a significant improvement of PFS, median OS substantially doubled compared to what has been reported in recent retrospective studies and, particularly, in the only other prospective trial (with the doublet lenalidomide-dexamethasone) so far conducted in transplant ineligible, elderly pts with pPCL (Musto P et al. Leukemia. 2014;28:222-5). This trial was registered at www.trialregister.nl (until June 2022) and https://trialsearch.who.int/ as NTR5350. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparative Effectiveness of Lenalidomide/Dexamethasone-Based Triplet Regimens for Treatment of Relapsed and/or Refractory Multiple Myeloma in Subgroups Defined By Cytogenetic Risk

Introduction: Patients with relapsed/refractory multiple myeloma (RRMM) and high cytogenetic risk have poor prognosis. Despite the proven efficacy of lenalidomide and dexamethasone (Rd)-based triplet regimens in the RRMM population, further investigation of these triplet regimens in RRMM patients with standard and high cytogenetic risk is needed to inform the optimal treatment approach for such patients, especially given the lack of head-to-head clinical trials for these regimens. This real-world study compared the effectiveness of Rd in combination with proteasome inhibitors, ixazomib (I), carfilzomib (K), and bortezomib (V), or monoclonal antibodies, elotuzumab (E) and daratumumab (D) with respect to treatment outcomes among RRMM patients in the United States (US) within subgroups defined by cytogenetic risk. Methods: The Flatiron Health Database (01/01/2014-09/30/2020) was used for this retrospective longitudinal study. Adult RRMM patients who initiated IRd, KRd, VRd, ERd, or DRd in line of therapy 2 or later (LOT2+) on or after 01/01/2014 were included. High cytogenetic risk was defined as the presence of del[17p], t[4;14], or t[14;16] by fluorescence in situ hybridization or karyotype tests. Patients with evidence of the tests but without the presence of these abnormalities were defined as standard risk. Index was the date of initiation for each LOT (multiple LOTs per patient were included); baseline was the 6-month period pre-index. Multivariable Cox proportional hazards models were used to compare duration of therapy (DOT), progression free survival (PFS), time to next therapy (TTNT), and overall survival (OS) between regimens. Patients who did not experience the event were censored at end of observation. Analyses were conducted separately in patients with high cytogenetic risk and in those with standard cytogenetic risk. Comparisons with ERd are not presented due to limited sample size. Results: A total of 1,185 patients contributed to 1,332 LOTs, of which 180 (13.5%) had high cytogenetic risk (IRd: n=36; KRd: n=41; VRd: n=58; ERd: n=13; DRd: n=32), 985 (73.9%) had standard cytogenetic risk (IRd: n=184; KRd: n=155; VRd: n=420; ERd: n=63; DRd: n=163), and 167 (12.5%) had unknown risk. In patients with standard cytogenetic risk, median age was 71 years and the majority (89.9%) of patients were treated in community settings; most regimens were in LOT2 (64.0%). Among these patients, DRd was associated with longer DOT compared to IRd (adjusted hazard ratio [95% confidence interval]: 1.85 [1.37, 2.50]), KRd (2.08 [1.53, 2.83]), and VRd (1.71 [1.26, 2.33]). Similarly, DRd was associated with prolonged PFS in comparison to all triplets (IRd: 1.78 [1.28, 2.46]; KRd: 1.86 [1.33, 2.61]; VRd: 2.31 [1.61, 3.34]), as well as longer TTNT (IRd: 1.79 [1.32, 2.44]; KRd: 1.91 [1.40, 2.61]; VRd: 1.54 [1.12, 2.11]). KRd was associated with shorter OS compared with DRd (1.59 [1.01, 2.49]). No other statistically significant differences were observed. In patients with high cytogenetic risk, del[17p] (55.6%) and t[4;14] (38.9%) were the most frequent cytogenetic abnormalities, while a smaller proportion of patients had t[14;16] (14.4%). Median age was 69 years and almost all patients (90.0%) were treated in community settings; most (63.9%) regimens were in LOT2. High risk patients appeared to have comparable outcomes across triplet regimens as no statistical significance was detected in any pair-wise comparisons. Comparative results are shown in Table 1.Conclusions: This real-world study assessed RRMM patients treated primarily within US community settings. In patients with standard cytogenetic risk, DRd was associated with statistically significantly better PFS, DOT, and TTNT than PI-containing Rd-based triplets and better OS compared to KRd. In patients with high cytogenetic risk, results suggest comparable effectiveness of Rd-based triplet regimens, although the interpretation of these results is limited by the small sample size. These findings highlight the importance of cytogenetic risk when making treatment recommendations for RRMM patients, while further elucidating the effectiveness of triplet therapies in routine clinical care. Among high risk patients, larger studies are needed to clarify the effectiveness of various Rd-triplets currently FDA-approved for the broader RRMM population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and safety of lenalidomide in diffuse large B-cell lymphoma: a meta-analysis of randomized controlled trials.

As an immunomodulatory agent with antitumor activity, lenalidomide has been evaluated for its value in diffuse large B-cell lymphoma (DLBCL). We performed a meta-analysis to gain a better understanding of the efficacy and safety of lenalidomide in DLBCL. PubMed, Cochrane Library, and Embase were searched up to March 2022 for potential studies. The pooled hazard ratio (HR) and relative risk (RR) with 95% confidence interval (CI) were estimated by the fixed/random effects model. Overall, 6 randomized controlled trials including 1938 patients were included. The complete response rate (CRR) of the group containing lenalidomide was 47.7% (95%CI 28.5-67.2%), which was higher than the 37.8% (95%CI 16.7-61.5%) of the control group without lenalidomide (RR = 1.11, 95%CI 1.03-1.20, P = 0.008). The overall estimation of survival showed a benefit for progression-free survival (PFS) (HR = 0.77, 95%CI 0.66-0.90, P = 0.001) but not overall survival (OS) or event-free survival (EFS). The lenalidomide group had a significant incidence of grade ≥ 3 hematological adverse events (AEs) involving neutropenia (RR = 1.56, 95%CI 1.15-2.11, P = 0.004) and febrile neutropenia (RR = 1.81, 95%CI 1.31-2.49, P < 0.001), with the incidence of neutropenia (48.3%, 95%CI 37.5-59.1%) being highest. In conclusion, addition of lenalidomide results in a higher CRR and better PFS but a higher incidence of grade ≥ 3 hematological AEs involving neutropenia and febrile neutropenia.

MM-171 Upfront Treatment Practice Patterns in Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy characterized by neoplastic plasma cells in the bone marrow and monoclonal paraprotein in the serum and urine. Treatment goals for MM address management of acute issues and prompt treatment to avoid further end-organ damage. The recent GRIFFIN trial (ASH 2020) demonstrated the efficacy (improved sCR and MRD) of daratumumab, lenalidomide, bortezomib, and dexamethasone (D-RVD) vs RVD without daratumumab in transplant eligible patients. Given the GRIFFIN trial's findings, this study was conducted to assess practice patterns and determine the most common upfront treatment physicians prescribe in their newly diagnosed, untreated MM patients. We conducted a survey of hematologist-oncologists actively treating MM in our region defined as Hudson Valley, upstate New York, and Southern Connecticut. Providers were informed of the region under study as well as the intended use for research for their voluntary participation. If no response was recorded, up to two follow-up requests were sent. 85 physicians were included in the study, and responses were recorded by email from 12/26/2021 to 02/13/2022. This study aims to measure the percentage of providers that have adopted the D-RVD protocol compared to other popular drug combinations indicated for MM one year after publication of the GRIFFIN trial results at ASH in December, 2020. Responses were recorded for 30 physicians and thus 35% of the population sample. There was a mean average of 1.4 requests to elicit provider response. Only 20% (6/30) of providers responded with D-RVD as their preferred front-line for standard-risk patients. The remaining 80% (24/30) preferred RVD without daratumumab as their standard upfront treatment. In the region under study, MM treating physicians have a disproportionately higher preference for the traditional RVD protocol compared to the more effective, although more recent, D-RVD protocol. This may reflect the need for a higher degree of research-informed practice among MM treating physicians within the region. Alternatively, given the fairly recent publication of the GRIFFIN trial, this finding may reflect the normal gap between published results and provider implementation of change in standard practice. Follow-up in late 2022 may demonstrate further permeation of this data as demonstrated in practice patterns.

Efficacy and safety of lenalidomide combined with bortezomib and dexamethasone induction therapy in newly diagnosed patients with multiple myeloma

Objective: This study aimed to evaluate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (VRD) in the treatment of newly diagnosed multiple myeloma (MM) . Methods: A total of 150 newly diagnosed patients with MM diagnosed in The First Affiliated Hospital of Soochow University from November 2018 to February 2021 and received VRD as the induction regimen were included to evaluate the safety and efficacy of VRD induction therapy for newly diagnosed MM. Results: The median follow-up was 22 months, two patients (1.3%) died early after treatment, and 148 patients (98.7%) completed induction therapy. 116 patients (77.3%) were mobilized to collect autologous hematopoietic stem cells, 101 cases (87.1%) were qualified in the collection, of which 48 cases (41.4%) were excellent in the collection. The 3-year progression-free survival (PFS) rate was 59%, and the 3-year overall survival (OS) rate was 83%. After induction, complete remission (CR) /stringent CR rate was 54.4%, ≥ very good partial remission rate was 77.3%, overall response rate was 86.0%, and minimal residual disease negative rate was 46.0%. There was no statistically significant difference in the efficacy of cytogenetic high-risk patients compared with standard risk patients (P=0.456) . The median PFS time of cytogenetic high-risk patients was shorter than that of standard risk patients (not reached vs 33 months, P=0.014) . There was no statistically significant difference in the median OS time (not reached vs not reached, P=0.072) . The highest incidence of hematological adverse events was thrombocytopenia (72%) , followed by neutropenia (42%) and anemia (20%) . The highest incidence of non-hematological adverse events was peripheral neuritis (56.7%) . The main digestive tract symptoms include constipation (30.0%) and diarrhea (17.3%) . Upper respiratory tract infection (23.3%) and lung infection (7.3%) are the main infections. The incidence of adverse thrombocytopenia (90.0% vs 63.7%, P=0.001) , neutropenia (54.2% vs 36.3%, P=0.038) , anemia (33.3% vs 13.7%, P=0.005) , diarrhea (27.1% vs 12.7%, P=0.030) , limb edema (20.8% vs 3.9%, P=0.030) , fever (20.8% vs 4.9%, P=0.006) , thrombosis (8.3% vs 0, P=0.016) , and renal function deterioration (20.8% vs 3.9%, P=0.030) in patients with renal insufficiency was higher than that in patients with normal renal function. Conclusion: The VRD regimen has a significant effect on newly diagnosed MM, does not affect the hematopoietic stem cell collection, and has controllable adverse events; however, the incidence of adverse events was higher in patients with renal insufficiency.

P-272: Efficacy and safety of ixazomib plus lenalidomide and dexamethasone following injectable proteasome inhibitor-based therapy in patients with relapsed/refractory multiple myeloma

P-272: Efficacy and safety of ixazomib plus lenalidomide and dexamethasone following injectable proteasome inhibitor-based therapy in patients with relapsed/refractory multiple myeloma

PPAR agonists attenuate lenalidomide's anti-myeloma activity in vitro and in vivo

Many patients with multiple myeloma (MM) have comorbidities and are treated with PPAR agonists. Immunomodulatory agents (IMiDs) are the cornerstones for MM therapy. Currently, little is known about how co-administration of PPAR agonists impacts lenalidomide treatment in patients with MM. Here, we determined the effects of PPAR agonists on anti-myeloma activities of lenalidomide in vitro and in a myeloma xenograft mouse model. Genetic overexpression and CRISPR/cas9 knockout experiments were performed to determine the role of CRBN in the PPAR-mediated pathway. A retrospective cohort study was performed to determine the correlation of PPAR expression with the outcomes of patients with MM. PPAR agonists down-regulated CRBN expression and reduced the anti-myeloma efficacy of lenalidomide in vitro and in vivo. Co-treatment with PPAR antagonists increased CRBN expression and improved sensitivity to lenalidomide. PPAR expression was higher in bone marrow cells of patients with newly diagnosed MM than in normal control bone marrow samples. High PPAR expression was correlated with poor clinical outcomes. Our study provides the first evidence that PPARs transcriptionally regulate CRBN and that drug-drug interactions between PPAR agonists and IMiDs may impact myeloma treatment outcomes.

Real-world Data From the Swiss Lenalidomide in MDS del(5q) (SLIM)-Registry Identify New Chances and Challenges in Lenalidomide Treatment of Patients With MDS del(5q).

Real-world Data From the Swiss Lenalidomide in MDS del(5q) (SLIM)-Registry Identify New Chances and Challenges in Lenalidomide Treatment of Patients With MDS del(5q).

PB2079: INTERIM REPORT OF BENDAMUSTINE PLUS RITUXIMAB AS FIRST-LINE INDUCTION THERAPY WITH OR WITHOUT LENALIDOMIDE MAINTENANCE THERAPY IN CHINESE PATIENTS WITH INHL OR EMCL: A MULTI-CENTER PROSPECTIVE TRIAL

Background: Bendamustine plus rituximab (BR) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma (iNHL) and elderly MCL (eMCL) based on the BRIGHT and STiL trials. But the data is rare from Chinese patients because the unavailability of bendamustine. Furthermore, the safety and efficacy of maintenance therapy with rituximab remained contradictory after BR induction therapy, due partly to the durable immuno-supression of bendumustine. On the other hand, lenalidomide, as a proven effective agent for iNHL and MCL, have immune modulatory function. So, as maintenance therapy after BR induction, lenalidomide may increase response rate and prolong progression free survival (PFS) for iNHL and eMCL. Aims: To assess the efficacy and safety of BR regimen for Chinese patients with iNHL and eMCL. And more importantly, to assess the efficacy and tolerability of lenalidomide as maintenance therapy after BR. Methods: We conducted a multi-institutional, prospective, non-randomized clinical trial for patients with iNHL and eMCL. The patients received standard six cycles of BR regimen as induction therapy, and then received lenalidomide (10mg, qd) maintenance vs. no maintenance, from December 2020 to February 2022. Patients with iNHL and elderly MCL who received at least two cycles of BR were evaluated. The primary endpoint of the study was progression-free survival (PFS). Results: Overall, 61 patients enrolled in the study, baseline characteristics of cohort were shown in Table 1. Median age at BR initiation was 55 years (range 24-74), 73.8% had ECOG 0-1, and 26.2% ECOG 2. Follicular lymphoma (FL) (62.3%) and marginalzone lymphoma (MZL) (24.6%) were the main subtypes of iNHL. The proportion of elderly MCL was 9.8%. Most patients were in stage 3 (9.8%) and stage 4 (72.1%). All patients have indication for systemic therapy. Till the date of February 10, 2022, a total of 85.2% completed 4 cycles induction therapy. Overall response was 94.2%, with 82.7% complete response (CR) and 11.5% partial remission (PR), (Figure 1). Progression during induction occurred only in one MCL patients. And another two patients with FL was suspected progressive disease during observation (no lenalidomide maintenance). After 4 cycles induction therapy, PET/CT detected in 40 patients (76.9%), while CT or MRI detected in 12 patients (19.7%). Among the 39 patients with complete remission assessed by PET-CT, 8 patients (20.5%) of them had residual lymph nodes with diameter > 1cm. So the CRR by CT is 67.3%, which is much higher than that reported in STiL study and BRIGHT study. The safety profile of BR regimen was shown in Table 2. Hematological toxicities was the main adverse events, with grade 3-4 neutropenia was recorded in 21.3%, febrile neutropenia in 8.2%, grade 3-4 anemia in 3.3%, and grade 3-4 thrombocytopenia in 1.6% of patients. The rate of fatigue, nausea/vomiting, skin rash and infections were less than 15%. A total of 40.0% patients proceeded to lenalidomide maintenance. However, 10% patients discontinued because of rash or other adverse reaction to lenalidomide. Image:Summary/Conclusion: BR regimen was feasible, safety and got high CRR for Chines iNHL and eMCL patients by our clinical trial. The efficacy and safety of maintenance lenalidomide after BR induction are still under follow-up. This trial was registered at http://www.chictr.org.cn. Clinical trial information: ChiCTR2200056288.

S178: SAFETY AND EFFICACY OF BELANTAMAB MAFODOTIN IN COMBINATION WITH RD IN NEWLY DIAGNOSED, TRANSPLANT INELIGIBLE MULTIPLE MYELOMA PATIENTS: A PHASE 1/2 STUDY BY THE HELLENIC SOCIETY OF HEMATOLOGY

Background: Belantamab mafodotin (belamaf), a multi-modal antibody-drug conjugate targeting BCMA, has shown efficacy and tolerability in pretreated patients (pts) with relapsed/refractory multiple myeloma. In pts refractory to immunomodulatory drugs, proteasome inhibitors, and antiCD38, belamaf plus pomalidomide and dexamethasone induced a very good partial response (VGPR) or better of 69.2% and a median progression-free survival of 16.2 months (Trudel S, ASH 2021). Preclinical evidence suggests that belamaf plus lenalidomide enhances antimyeloma activity, with no overlapping toxicities. Aims: To evaluate the safety and efficacy of belamaf plus lenalidomide and dexamethasone (Rd) in transplant-ineligible (TI) pts with newly diagnosed multiple myeloma (NDMM). Methods: The ongoing, prospective, open-label, 2-part, phase 1/2 BelaRd study (NCT04808037) aims to enroll 66 pts with TI NDMM from a Greek center. Eligible are adult pts with Eastern Cooperative Oncology Group status 0–2 and adequate organ function. Part 1 (dose selection) evaluates the safety/tolerability of 3 belamaf doses (2.5, 1.9, and 1.4 mg/kg on Day 1 of every other 28-day cycle) plus Rd (each dose regimen administered to a cohort of 6 pts) over ≥4 weeks of follow up; subsequently, an additional 6 pts are enrolled in each dose cohort to establish the recommended phase 2 dose (RP2D). Part 2 (dose expansion) evaluates the safety and clinical activity of belamaf RP2D plus Rd in 30 additional pts. This descriptive analysis presents the safety data for all Part 1 pts and the efficacy data for all Part 1 pts with ≥2 post-baseline efficacy assessments by the cut-off date (14/01/2022). Results: Of 36 pts included, 35 (97.2%) continued study treatment by the cut-off date, and 1 (2.8%) had died due to a belamaf unrelated adverse event (AE). The pt median age was 72.5 years (range 64.0–86.0). Of pts with available data (30 [83.3%]), pts at revised International Staging System stages I, II, and III were 6 [20.0%], 21 [70.0%], and 3 [10.0%], respectively, and 3 (10.0%) had high-risk cytogenetics (i.e., del17p13, t(4;14), t[14;16]). Median duration of therapy was 4.2 months (range 0.5–11.9) and median number of cycles reached was 5.0 (range 1.0–11.0). Twenty-two (61.1%) pts experienced at least one grade (Gr) 3–4 AE. One (2.8%) pt experienced a Gr 5 AE (pneumonia), unrelated to belamaf. Most common (≥ 10.0% of pts) Gr 3–4 AE were fatigue (13 [36.1%] pts), visual acuity reduced (6 [16.7%] pts), and rash (5 [13.9%] pts). Gr 3–4 thrombocytopenias and infections were not reported, as were any Gr infusion-related reactions (Table). Pts with Gr 1–2 ocular symptoms, visual acuity reduced, and keratopathy, were 27 (75.0%), 21 (58.3%), and 18 (50.0%), respectively. Pts with Gr 3–4 ocular symptoms, visual acuity reduced, and keratopathy were 0 (0.0%), 5 (13.9%) and 0 (0.0%), respectively. Of all pts, 28 (77.8%) were evaluable for efficacy (Table). At a median follow up of 4.2 months (range 0.5–11.9), the overall response rate was 96.4% (27/28 pts; complete response [CR]: 14.3% [4/28 pts]; VGPR: 35.7% [10/28 pts]; partial response [PR]: 46.4% [13/28 pts]); no disease progression was reported. Of pts achieving VGPR, 6/10 (60.0%) had negative status serum/urine immunofixation electrophoresis. Median time to PR or better was 1.0 months (range 0.9–2.0). Image:Summary/Conclusion: In pts with TI NDMM, belamaf every 2 months plus Rd showed an improved safety profile, especially at lower doses. Rapid and deep hematological responses were recorded.

CELESTIMO: A phase III trial evaluating the efficacy and safety of mosunetuzumab plus lenalidomide versus rituximab plus lenalidomide in patients with relapsed or refractory follicular lymphoma who have received ≥ 1 line of systemic therapy.

TPS7588 Background: Despite significant progress with first-line immunochemotherapy, most patients with follicular lymphoma (FL) will eventually relapse with increasing refractoriness and decreasing duration of response to subsequent therapy lines (Rivas-Delgado et al. 2019). Mosunetuzumab (M) is a CD20xCD3 bispecific antibody that engages and redirects T-cells to eliminate malignant B cells (Sun et al. 2015). In an ongoing, pivotal Phase I/II trial of M monotherapy, patients with relapsed/refractory (R/R) FL who have received ≥2 prior treatment lines achieve deep and durable responses (NCT02500407; Budde et al. ASH 2021). Preliminary data from a Phase Ib study have suggested favorable safety and promising activity of M in combination with lenalidomide (Len), a potent immunomodulatory agent that has shown additive/synergistic activity with an anti-CD20 antibody in R/R indolent lymphoma (Leonard et al. 2019), in patients with R/R FL who have received ≥1 prior therapy (NCT04246086; Morschhauser et al. ASH 2021). The chemotherapy-free M-Len combination may represent a promising outpatient therapy option for future management of patients with R/R FL. The randomized, multicenter Phase III study has been initiated. Methods: CELESTIMO (NCT04712097) is a randomized, multicenter, open-label Phase III study evaluating the efficacy and safety of M-Len versus rituximab plus Len (R-Len) in patients with previously treated R/R FL. Patients must have histologically documented CD20+ FL (Grades 1–3a) requiring systemic therapy and have received ≥1 prior line of systemic therapy. Patients are randomized (1:1) to receive M-Len (M intravenously [IV] on Days [D] 1, 8 and 15 of Cycle [C] 1 [21-day cycle] and D1 of C2–12 [28-day cycles], plus Len orally [PO] on D1–21 of C2–12) or R-Len (R IV on D1, 8, 15 and 22 of C1 then on D1 of C3, 5, 7, 9, and 11, plus Len PO on D1–21 of C1–12 [all 28-day cycles]), and stratified by disease progression within 24 months of initial treatment (yes/no), number of prior lines of therapy (1 versus ≥2), and refractoriness to anti-CD20 therapy (refractory/non-refractory). The primary endpoint is progression-free survival (PFS) assessed by independent review committee; secondary endpoints include investigator-assessed PFS, complete and objective response, overall survival, and safety. Biomarkers predictive of response to M-Len and R-Len will also be investigated as exploratory endpoints. The study started recruitment in 2021 and plans to enroll ̃400 patients from approximately 16 countries and 150 sites globally. Clinical trial information: NCT04712097.

Clinical Efficacy of Lenalidomide Combined with Cyclophosphamide and Dexamethasone in the Treatment of Multiple Myeloma

Objective: Multiple myeloma has a great impact on patients; the use of implant denture restorative treatment is ideal, and it is vital to carry out scientific treatment methods. Methods: The research subjects were inclusive of 60 patients with multiple myeloma, who were randomly selected from January 2019 to December 2019. The patients were divided into a study group and a control group, with 30 patients in each group. The patients in the control group were treated with conventional treatment, while the patients in the study group were treated with lenalidomide combined with cyclophosphamide and dexamethasone. The effectiveness of treatment, adverse effects, and clinical indices of the two groups were compared. Results: Comparing different treatment methods, the differences in the indices between the two groups were statistically significant (p &lt; 0.05). Conclusion: The use of lenalidomide combined with cyclophosphamide and dexamethasone in the treatment of patients with multiple myeloma increases the effectiveness of treatment and improves patients’ clinical indices; thus, it is worthy of promotion.

Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study.

In RE-MIND2 (NCT04697160), patient-level outcomes from the L-MIND study (NCT02399085) of tafasitamab plus lenalidomide were retrospectively compared with patient-level matched observational cohorts treated with National Cancer Care Network (NCCN)/European Society for Medical Oncology (ESMO)-listed systemic therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data were collected from health records of eligible patients aged ≥18 years with histologically confirmed DLBCL who had received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients from L-MIND were matched with patients from the RE-MIND2 observational cohort using estimated propensity score-based 1:1 nearest-neighbor matching, balanced for nine covariates. The primary analysis compared tafasitamab plus lenalidomide with patients who received any systemic therapy for R/R DLBCL (pooled in one cohort) or bendamustine plus rituximab (BR) or rituximab plus gemcitabine and oxaliplatin (R-GemOx; as two distinct cohorts). The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and time-to-event outcomes. In RE-MIND2, 3,454 patients were enrolled from 200 sites in North America, Europe, and Asia-Pacific. Strictly matched pairs of patients consisted of tafasitamab plus lenalidomide versus systemic therapies pooled (n = 76 pairs), versus BR (n = 75 pairs), and versus R-GemOx (n = 74 pairs). Significantly prolonged OS was reported with tafasitamab plus lenalidomide versus systemic pooled therapies [hazard ratios (HR): 0.55; P = 0.0068], BR (HR: 0.42; P < 0.0001), and R-GemOx (HR: 0.47; P = 0.0003). RE-MIND2, a retrospective observational study, met its primary endpoint, demonstrating prolonged OS with tafasitamab plus lenalidomide versus BR and R-GemOx. See related commentary by Cherng and Westin, p. 3908.

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.

Clinical Efficacy of Lenalidomide Combined with Bortezomib in the Treatment of Multiple Myeloma Nephropathy

Multiple myeloma combined with nephropathy is one main cause of death in patients; we started this study to discuss the clinical efficacy and incidence of adverse effects of lenalidomide combined with bortezomib in multiple myeloma nephropathy treatment. We randomly selected eighty multiple myeloma nephropathy patients in Hematology Department of the First People’s Hospital of Taizhou City from March 2020 to September 2021, then divided them into observation group (40 cases received lenalidomide combined with bortezomib treatment) and control group (40 cases received bortezomib treatment). Compared both groups on serum immunoglobulin, light chain protein concentration, blood creatinine, blood uric acid and nephropathy before and after therapy and also compared the clinical efficiency and the occurrence of adverse reactions. Observation group possessed remarkably higher clinical efficiency (92.5 %) than control group (82.5 %) (p<0.05); it possessed obviously smaller decrease of immunoglobulin, light chain protein concentration level, serum creatinine, blood calcium and blood uric acid than control group (p<0.05); its adverse reactions occurrence (17.5 %) had no obvious dereference from control group (20.0 %) (p<0.05); its adverse reactions rate (17.5 %) had no obvious dereference from control group (20.0 %) (p<0.05). Lenalidomide combined with bortezomib has better clinical efficacy in treating multiple myeloma nephropathy, can effectively improve renal function, has greater clinical efficacy and does not increase adverse reactions rate, so it is worth popularizing in clinic.

MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma

AbstractBiomarkers that predict response to lenalidomide maintenance therapy in patients with multiple myeloma (MM) have remained elusive. We have shown that immunomodulatory drugs (IMiDs) exert anti-MM activity via destabilization of MCT1 and CD147. In this study, cell samples of 654 patients with MM who received lenalidomide (n = 455), thalidomide (n = 98), or bortezomib (n = 101) maintenance were assessed by gene expression profiling and RNA sequencing, followed by correlation of MCT1 and CD147 expression with data for progression-free survival (PFS) and overall survival (OS). Patients with high expression levels of MCT1 showed significantly reduced PFS (31.9 months vs 48.2 months in MCT1high vs MCT1low; P = .03) and OS (75.9 months vs not reached [NR] in MCT1high vs MCT1low; P = .001) in cases with lenalidomide maintenance, whereas MCT1 expression had no significant impact on PFS or OS in cases with bortezomib maintenance. We validated the predictive role of MCT1 for IMiD-based maintenance in an independent cohort of patients who received thalidomide (OS, 83.6 months vs NR in MCT1high vs MCT1low; P = .03). Functional validation showed that MCT1 overexpression in human MM cell lines significantly reduced the efficacy of lenalidomide, whereas no change was observed with bortezomib treatment, either in vitro or in a MM xenograft model. Our findings have established MCT1 expression as a predictive marker for response to lenalidomide-based maintenance in patients with MM.

Lenalidomide Dosing and Outcomes in Transplant-Ineligible Patients with Newly-Diagnosed Multiple Myeloma: A Multi-Institutional Report from the Canadian Myeloma Research Group (CMRG) Database

Lenalidomide Dosing and Outcomes in Transplant-Ineligible Patients with Newly-Diagnosed Multiple Myeloma: A Multi-Institutional Report from the Canadian Myeloma Research Group (CMRG) Database

Zanubrutinib, Lenalidomide Plus R-CHOP (ZR 2-CHOP) As the First-Line Treatment for Diffused Large B-Cell Lymphoma (DLBCL)

IntroductionTo evaluate the safety and efficacy of zanubrutinib, lenalidomide plus R-CHOP (ZR 2-CHOP) as the first-line treatment for DLBCL patients, we conducted this single-arm retrospective observational study.MethodsTreatment-naïve patients with DLBCL(including but not limited to double-hit, double expression) aged 18 to 75 years were enrolled.ZR 2-CHOP was given as follows, Oral zanubrutinib was given continuously (160 mg twice daily) from Day 0, lenalidomide 25 mg daily Day 1-7. Patients were administered intravenously rituximab (375 mg/m 2 Day 0), cyclophosphamide (750 mg/m 2 Day 1), doxorubicin (50 mg/m 2 Day 1), vincristine (1.4 mg/m 2 Day 1), and oral prednisone (100 mg Day 1-5). All patients were recommended to receive 6 cycles of ZR 2-CHOP (R-CHOP or R 2-CHOP were allowed in cycle 1-2 due to poor physical condition at treatment) and patients older than 70 years old were administered ZR 2-miniCHOP (Figure 1). CT or PET-CT scans were applied to mid-term efficacy and PET-CT scan was conducted after 6 cycles. ctDNA was dynamically detected before treatment, after 3 and 6 cycles to evaluate tumor mutational burden. The primary endpoint was complete response ratio (CRR) at mid-term and after 6 cycles. The secondary endpoint was overall response rate (ORR), ctDNA dynamics and adverse events (AE). AEs were graded based on CTCAE (version 5.0).Results12 treatment-naïve DLBCL patients diagnosed in Pukou CLL Center were enrolled in this cohort between July 2020 and June 2021. The median age was 56 years old and all patients had ECOG-PS ≤2. 1 patient (1/12) was diagnosed as double-hit DLBCL and 9 patients (9/12) as double-expression. 10 patients were non-GCB and 2 were GCB. 7 patients were classified as high-intermediate and high-risk group according to NCCN-IPI (Table 1). At data cutoff (1st July, 2021), the median follow-up was 8 months (3-12 months) with all patients have completed at least 3 cycles and mid-term assessment has been conducted. The ORR was 100.0%, with 10 patients achieved CR and 2 patients achieved PR (both two patients received R-CHOP regimen in cycle 1/cycle 1-2 due to poor physical condition at initial treatment, Figure 1). 10 patients have received 6 cycles, all of them achieved CR (Figure 2). ctDNA was dynamically detected in six patients. The median number of detectable ctDNA mutation among six patients was 8 (0-12) with two patients classified as MCD subtype and one patients as EZB subtype. All six patients showed undetectable ctDNA after 3 cycles. During end of treatment follow-up, one patient (triple-hit, EZB) who scheduled to receive auto-SCT underwent disease progression 4 months later and reemergence of ctDNA showed previous homologous clones. The most common hematological toxicity events were lymphocytes count decreased, neutrophil count decreased, thrombocytopenia and anemia, with 3-4 level occurrence rate was 66.7%, 25.0%, 25.0% and 16.7%. The most common non-hematological toxicity events were nausea, fatigue and anorexia. One patients discontinued oral zanubrutinib and lenalidomide in last two cycles due to drug rash.ConclusionZR 2-CHOP could attain high CR rate and ctDNA clearance in TN DLBCL, including patients with DEL and/or high-risk. The overall tolerability was manageable. ZR 2-CHOP could be one of the promising choice for TN DLBCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:Zanubrutinib was used in the initial treatment of high-risk DLBCL.

Retrospective Comparison of the Efficacy and Safety of Lenalidomide, Bortezomib and Dexamethasone (RVD) 21-Day Schedule Vs. 28-Day Schedule in Patients with Newly Diagnosed Multiple Myeloma

Background. Based on the IFM 2009 trial, lenalidomide, bortezomib, dexamethasone (RVD) induction regimen, followed by autologous stem-cell transplantation has been the cornerstone of the treatment for newly diagnosed, transplant eligible multiple myeloma (MM) patients for many years. The treatment has been used because it allows for achievement of a deep remission in the majority of patients before stem cell collection which has been shown to be of benefit for the prognosis of patients. While this is a standard approach to induction, there are many variations in dosing. Two of the most common schedules are an RVD-21 (lenalidomide days 1-14, bortezomib days 1,4,8,11) and an RVD-28 (lenalidomide days 1-21, bortezomib weekly for three weeks). Despite the broad use of this regimen in myeloma therapy, there has been limited data that compare the efficacy and safety of these variations of RVD. This is a retrospective analysis of patients treated at a single center that compares the safety and efficacy of both schedules in newly diagnosed multiple myeloma.Methods. Patients were assigned into two groups based on the prescribed treatment schedule: RVD-21 or RVD-28. The primary endpoint of this study is overall survival (OS). Secondary endpoints include progression-free survival (PFS) at first relapse (PFS-1) and at second relapse (PFS-2) and time to very good partial response (VGPR). Safety outcomes are evaluated via the incidence and severity of adverse events. OS and PFS were summarized by variables of interest using standard Kaplan-Meier methods. Multivariable Cox regression was performed to adjust for potential confounding variables. VGPR or better response rates and adverse events between two groups were compared using Fisher's exact test.Results. A total of 92 patients were included in the analysis, 67 patients were started on RVD-21 and 25 on RVD-28. Four patients were switched from RVD-21 to RVD-28, and 2 patients were switched from RVD-28 to RVD-21. The median follow-up was 2.8 months. No difference was found in OS between the two RVD schedules in the univariate analysis, with median survival of 27.6 months in the RVD-21 and 31.1 months in RVD-28 (P=0.668) (Figure 1). Median PFS-1 (C1D1 to death or first progression) observed was 35.1 months in patients on RVD-21 and 23.0 months in patients on RVD-28 (p=0.492). Median PFS-2 (C1D1 to death or second progression) observed was 35.0 months in patients treated with RVD-21 and 24.6 months in patients treated with RVD-28 (p=0.404). No statistically significant difference was noted in overall response rate, with 72.1% patients in RVD-21 and 62.5% patients in RVD-28 achieving VGPR or better (p=0.442). Time to VGPR analysis did not yield a statistically significant difference between the two RVD schedules (2.3 months in RVD-21 and 2.8 months in RVD-28) (p= 0.104). For each outcome, baseline variables with p<0.1 in the univariate analyses were adjusted in the Cox regression models with RVD schedule as the independent variable. No significant associations were found between RVD schedule and OS, PFS-1, PFS-2 or time to VGPR. These findings were consistent with the univariate analyses. No statistically significant differences in the incidence of adverse events were found in patients in either of the treatment . Among the patients treated with RVD-21, 23.5% reported any grade of neuropathy compared to 16.7% of patients treated with RVD-28 (p=0.575) (Table 1).Conclusion. No differences in efficacy and safety outcomes were found among the RVD-21 and RVD-28 treatment schedules supporting individualized approach to induction schedule based on patient's ability to tolerate therapy. Shorter therapy schedules in RVD-21 allow for faster time to transplant, however, the time to achieve VGPR was not different. [Display omitted] DisclosuresHillengass: Beijing Medical Award Foundation: Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Skyline: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Axxess Network: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Curio Science: Speakers Bureau; Beijing Life Oasis Public Service Center: Speakers Bureau.

Efficacy of Daratumumab, Lenalidomide, and Dexamethasone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma and Impaired Renal Function from the Phase 3 Maia Study Based on Lenalidomide Starting Dose

Efficacy of Daratumumab, Lenalidomide, and Dexamethasone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma and Impaired Renal Function from the Phase 3 Maia Study Based on Lenalidomide Starting Dose