Novel Targeted Therapies and Their Impact on Survival from Multiple Myeloma (MM) and Chronic Lymphocytic Leukaemia (CLL) in the Real World

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3546-3546
Author(s):  
Alexandra G Smith ◽  
Timothy Bagguley ◽  
Eve Roman ◽  
Andy C Rawstron ◽  
James R Bailey ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Chronic Lymphocytic Leukaemia ◽  
Combination Chemotherapy ◽  
Real World ◽  
Research Funding ◽  
Lymphocytic Leukaemia ◽  
Alkylating Agents ◽  
First Line ◽  
Time Periods ◽  
Line Chemotherapy

Abstract Introduction The treatment landscape for many mature B-cell malignancies is evolving rapidly, with patients and clinicians facing increasingly complex choices about therapeutic options that differ in efficacy, toxicity and cost. Accounting for around a quarter of all haematological cancer diagnoses, multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) are two conditions where increases in the number and combinations of potentially life-prolonging therapies has been particularly marked; ranging from the use of single alkylating agents to immunomodulatory drugs and proteasome inhibitors for MM, and combination chemotherapy, immuno-chemotherapy, novel monoclonal antibodies and tyrosine-kinase inhibitors (TKIs) for CLL. Contemporary data enabling the success of such therapeutic changes to be evaluated in the general patient population is, however, lacking. With centralized diagnostics and a unified clinical network covering a catchment population of 4 million, the UK's Haematological Malignancy Research Network (www.hmrn.org) was specifically established to provide timely real-world data to answer such questions; and findings from this unique population-based cohort are reported here. Methods Patients newly diagnosed 2004-13 with MM (n=2084) or CLL (n=1866) were followed-up until January 2016. Demographic, prognostic, first-line treatment and outcome data for the time-periods 2004-07, 2008-10 and 2011-15 were examined using standard statistical methods; relative survival (RS) was estimated using national life tables. Results The median age at diagnosis of MM was 73 years (17% <60 years); 39% of patients presented with an ISS score of III and 25% were asymptomatic (CRAB score 0). In total, 1514 (73%) patients received first-line chemotherapy either at diagnosis or as a consequence of disease progression. Regimens were classified by their main agent, and the therapy changes over the 11-year period are shown in Figure 1a; in 2004-07, 44% of treated patients received single-agent alkylating therapy, in 2008-10 76% were treated with combination immunomodulatory therapy and by 2011-15 this had increased to 92%. The 3-year overall survival (OS) and RS estimates for all patients combined were 45.9% (95% Confidence Interval 43.4-48.4) and 52.0% (49.1-54.8) respectively. Differences in outcome by treatment year are clearly evident (Figure 1b): 3-year RS 2004-07, 46.5% (41.8-51.2); 2008-10, 48.4% (43.5-53.2); and 2011-15, 62.1% (56.8-66.9). The improvement in survival for patients treated in 2011-15 compared to 2004-07 was confirmed by multivariate Cox regression (Hazard Ratio 0.65, 0.56-0.76). With a median diagnostic age of 71 years (18% <60 years); the majority of CLL patients had early-stage disease (BinetStage A, 78%). In total 547 patients were treated with first-line chemotherapy, with the regimen again changing over time (Figure 1c). Patients treated 2004-07 generally received single alkylating agents (56%) or combination chemotherapy (42%), by 2008-10 32% of patients had a monoclonal antibody added to chemotherapy (chemo-immunotherapy), increasing to 72% among those treated 2011-15. The 3-year OS and RS for all treated patients combined were 69.5% (65.3-73.3) and 80.3% (75.5-84.3) respectively. However, there was no incremental statistically significant change in 3-year RS (Figure 1d); 2004-07, 76.4% (65.2-84.4); 2008-10, 78.3% (69.8-84.6); and 2011-15 84% (76.3-89.4); and taking 2004-07 as the reference, the corresponding hazard ratios for the 3 time-periods were 1 (reference), 1.00 (0.78-1.37) and 0.79 (0.58-1.09). The cost implications of the changing treatment landscape are currently being examined, and by December 2016 the findings presented above will include more recently diagnosed patients (2014-15), which is particularly pertinent for CLL, where a step-change may have occurred due to the introduction of TKIs. Conclusions Our analyses confirm that first-line chemotherapy for MM and CLL is changing markedly; highlighting the importance of monitoring the impact of therapeutic change in a real-world setting. The improvement in MM survival currently contrasts with CLL, suggesting that encouraging results from clinical trials may not always translate directly into similar improvements at a population level. Clearly, additional analysis of data from patients diagnosed >2014 are required. Figure 1 Figure 1. Disclosures Smith: Novartis: Research Funding; Janssen-Cilag: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Cook:Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Glycomimetics: Consultancy. Patmore:Roche: Honoraria; Janssen Cilag: Honoraria.

scholarly journals Real-World Treatment Patterns from the HUMANS Study in Multiple Myeloma in Denmark

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5030-5030
Author(s):  
Niels Abildgaard ◽  
Anders Waage ◽  
Markus Hansson ◽  
Pekka Anttila ◽  
Mate Szilcz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Treatment Duration ◽  
Research Funding ◽  
Population Based ◽  
Treatment Patterns ◽  
Line Treatment ◽  
First Line ◽  
Real World Evidence ◽  
First Line Treatment

Introduction Current treatment for multiple myeloma (MM), an incurable but treatment sensitive plasma cell cancer, aims to extend time to disease progression, prolong survival and improve quality of life. Nevertheless, epidemiological knowledge regarding MM treatment is mostly derived from randomized controlled trials, which are limited by strict inclusion criteria, study designs that assess drug efficacy in optimal clinical settings, and short follow-up. Current treatment options for MM are associated with complex and varying treatment-related side effect profiles. However, real-world evidence is available only for a limited selection of treatment regimens. Thus, there is a need for studies to further investigate treatment patterns in clinical settings that reflect real-world practice. The Health Outcome and Understanding of Myeloma - a multi-national real-world evidence (HUMANS) study - aimed to characterize patient characteristics, treatment patterns, and outcomes for newly diagnosed patients with MM who received first-line treatment. Here we report first results from the Danish study. Methods This population-based, retrospective, longitudinal, observational study used secondary data from the Danish Cancer Register (DCR) and National Patient Register (NPR) for patients diagnosed with MM. Patients were stratified by autologous stem cell transplantation (ASCT) and pharmacological treatment (bortezomib-based, lenalidomide-based, or other first-line therapy) and characterized using descriptive statistics. To analyse recent treatment patterns and also include patients with long duration before treatment start, eligible patients had first MM diagnosis from 2005-2016 in the NPR and DCR (diagnosis date identified from the DCR), first MM-specific treatment from 2010-2018 in the NPR, no other hematologic cancer records in the NPR and DCR, and no MM treatment before diagnosis. Treatment duration (time between start and end of treatment period, with set grace period of 60 days and assumed treatment supply of 7 and 28 days per treatment event for bortezomib and lenalidomide, respectively) and overall survival (OS) were estimated by Kaplan-Meier method. Results The study population comprised 2,451 patients with MM, of which 887 patients (36%) underwent ASCT. In the non-ASCT population (n=1564), the majority (n=838, 54%) received bortezomib as first-line treatment, 102 patients (7%) received lenalidomide, and for 631 patients (40%), first-line treatment could not be identified (referred to as the other non-ASCT cohort). Mean (standard deviation) age overall at first MM diagnosis was 68 (±11) years, and was 72 (±8), 75 (±9), 77 (±7), and 59 (±8) years in the bortezomib, lenalidomide, other non-ASCT and ASCT cohorts, respectively. A higher number of men (57%) than women were diagnosed with MM. From 2015 onwards, the proportion of patients who received lenalidomide increased, whereas for patients who received other MM specific drugs, the proportion decreased (see Table 1). The median OS (95% confidence interval [CI]) from administration of first-line treatment for the bortezomib and lenalidomide cohorts was 52.9 (46.2-58.2) and 69.3 (54.7-108.4) months, respectively. For the ASCT cohort the median OS was 117.2 (104.2-133.8) months from MM diagnosis. Patients followed a once or twice weekly regimen of bortezomib treatment, i.e. 3/4 or 7 days between treatments (Figure 1). Patients in the bortezomib cohort remained treated with a median bortezomib treatment duration of 4 months (CI 4.04-4.60) and an estimated 10% remained on treatment at 10 months. In the lenalidomide cohort, patients remained treated with a median duration of 7 months (CI 4.67-10.12) and an estimated 10% remained on treatment at 23 months (Figure 2). Conclusion In this study, we present population-based treatment patterns and outcomes for MM in Danish clinical practice. The 4 month median treatment duration of bortezomib was lower than the target treatment suggested by prior clinical trials. The differences in overall survival and treatment duration should be interpreted with caution, as patients in the different cohorts have varying baseline characteristics. Linked data from the DCR and NPR may provide real-world evidence of treatment patterns in clinical practice. Research regarding time to progression in a multiple myeloma real-world setting is warranted. Disclosures Abildgaard: Amgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Celgene: Research Funding. Szilcz:Parexel International: Employment. Ma:Parexel International: Employment. Ørstavik:Takeda Pharmaceuticals International AG: Employment. Bent-Ennakhil:Takeda Pharmaceuticals International AG: Employment. Freilich:Parexel International: Employment. Gavini:Takeda Pharmaceuticals International AG: Employment.

Characteristics of Patients Presenting with Secondary Myelodysplastic Syndrome During Treatment with Lenalidomide for Relapsed/Refractory Multiple Myeloma: 5q Deletions Can Be Observed

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1876-1876 ◽  
Author(s):  
Rashmi S. Goswami ◽  
David Barth ◽  
Esther Masih-Khan ◽  
Haowei (Linda) Sun ◽  
Manoj Mathew ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Myelodysplastic Syndrome ◽  
Median Time ◽  
Research Funding ◽  
Alkylating Agents ◽  
Chromosome 5 ◽  
First Line ◽  
Line Therapy ◽  
Previously Treated ◽  
Secondary Mds

Abstract Abstract 1876 Multiple myeloma (MM) is a neoplastic process involving plasma cells and the second most common hematologic malignancy after lymphoma. The relative survival rates for MM have been increasing over the last three decades, from 26% in the 1970s to 35% in recent years, due to the introduction of autologous stem cell transplantation (ASCT), and more recently, the introduction of novel agents. Among patients (pts) diagnosed with MM between 1997 and 2006, those who received at least one of the novel agents thalidomide, lenalidomide and bortezomib had double the median survival compared to those who did not receive any of these treatments (Kumar SK, Blood, 2008). Given that improvements are being made in the survival of myeloma pts, they may be more prone treatment-related complications, including treatment-related myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Herein we report seven cases of secondary MDS occurring in MM pts during treatment with lenalidomide-based (len-based) therapy for relapsed/refractory (rel/ref) MM. The pts examined were diagnosed with MM between 2000 and 2006, and consisted of 5 males and 2 females, ranging from 56–79 years of age (median age: 69 years). Five of the seven pts had undergone ASCT whereas the remaining two pts were treated with oral alkylating agents (cyclophosphamide/prednisone or melphalan/dexamethasone) as first-line treatment; one pt received another ASCT as second-line therapy. All pts received len-based regimens as second, third, or fourth-line therapy. The median time to development of MDS after diagnosis of MM was 70.5 months (range: 43.7 to 115.3 months). Of the pts that received ASCT as part of first-line therapy, the median time to development of MDS was 49.9 months (range: 35.6 to 76.1 months) post ASCT, while the median time to development of MDS after initiation of len-based treatment was 19.2 months (range: 1.1 to 33.8 months). All pts presented with decreasing blood counts at the time of MDS diagnosis; at this time the median hemoglobin level was 94 g/L (range 67–107 g/L), ANC 1.7 × 109/L (range 0.9–8.2 × 109/L) and platelet count 62 × 109/L (range 11–148 × 109/L) and only 1 pt had circulating blast cells. Pathological examination of blood films, bone marrow aspirates and biopsies confirmed the presence of MDS in all pts (4 pts with refractory cytopenia with multilineage dysplasia, 2 of whom also had ringed sideroblasts, 2 pts with refractory cytopenia with unilineage dysplasia, and 1 pt with refractory anemia with excess blasts-II); three had concomitant MM in the marrow. Of interest, 3 pts with evidence of dysmegakaryopoiesis demonstrated the presence of hypolobated megakaryocytes, similar to that seen in 5q- syndrome. Conventional cytogenetics demonstrated complex karyotypes in 6 pts, and 4 had structural abnormalities of chromosome 5, with deletion of the long arm, including 2 of the 3 pts with megakaryocyte hypolobation. Four of the 7 pts also had abnormalities involving chromosome 7, including deletion of 7q. In addition, 2 pts had deletions of chromosome 17 including deletion of TP53 (17q13). Although len may be a simple bystander in the development of MDS in rel/ref MM pts previously treated with alkylating agents, the observation of chromosome 5 abnormalities, including 5q deletion, is of note. Therefore, despite its established efficacy in the treatment of MDS, as well as of MM, len may not be able to protect against the development of MDS in pts previously treated with alkylating agents. As in other malignancies in which prolonged survival has been achieved, the increased life span of MM pts mandates monitoring for late complications of therapy. A progressive decrease in peripheral blood counts during treatment with len-based regimens warrants consideration of secondary MDS. Disclosures: Chen: Celgene Corporation: Consultancy, Honoraria, Research Funding. Trudel:Celgene: Honoraria. Reece:Celgene: Honoraria, Research Funding.

scholarly journals Real World Treatment Patterns and Toxicity Among Elderly Patients with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5571-5571
Author(s):  
Jesus D Gonzalez-Lugo ◽  
Ana Acuna-Villaorduna ◽  
Joshua Heisler ◽  
Niyati Goradia ◽  
Daniel Cole ◽  
...  
Keyword(s):  
Side Effects ◽  
Real World ◽  
Research Funding ◽  
Treatment Patterns ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Treatment Change ◽  
Free Survival ◽  
First Line Treatment

Introduction: Multiple Myeloma (MM) is a disease of the elderly; with approximately two-thirds of cases diagnosed at ages older than 65 years. However, this population has been underrepresented in clinical trials. Hence, there are no evidence-based guidelines to select the most appropriate treatment that would balance effectiveness against risk for side effects in the real world. Currently, guidelines advise that doublet regimens should be considered for frail, elderly patients; but more detailed recommendations are lacking. This study aims to describe treatment patterns in older patients with MM and compare treatment response and side effects between doublet and triplet regimens. Methods: Patients diagnosed with MM at 70 years or older and treated at Montefiore Medical Center between 2000 and 2017 were identified using Clinical Looking Glass, an institutional software tool. Recipients of autologous stem cell transplant were excluded. We collected demographic data and calculated comorbidity burden based on the age-adjusted Charlson Comorbidity Index (CCI). Laboratory parameters included cell blood counts, renal function, serum-protein electrophoresis and free kappa/lambda ratio pre and post first-line treatment. Treatment was categorized into doublet [bortezomib/dexamethasone (VD) and lenalidomide/dexamethasone (RD)] or triplet regimens [lenalidomide/bortezomib/dexamethasone (RVD) and cyclophosphamide/bortezomib/dexamethasone (CyborD)]. Disease response was reported as VGPR, PR, SD or PD using pre-established criteria. Side effects included cytopenias, diarrhea, thrombosis and peripheral neuropathy. Clinical and laboratory data were obtained by manual chart review. Event-free survival was defined as time to treatment change, death or disease progression. Data were analyzed by treatment group using Stata 14.1 Results: A total of 97 patients were included, of whom 46 (47.4%) were males, 47 (48.5%) were Non-Hispanic Black and 23 (23.7%) were Hispanic. Median age at diagnosis was 77 years (range: 70-90). Median baseline hemoglobin was 9.4 (8.5-10.5) and 14 (16.1%) had grade 3/4 anemia. Baseline thrombocytopenia and neutropenia of any grade were less common (18.4% and 17.7%, respectively) and 11 patients (20%) had GFR ≤30. Treatment regimens included VD (51, 52.6%), CyborD (18, 18.6%), RD (15, 15.5%) and RVD (13, 13.4%). Overall, doublets were more commonly used than triplets (66, 68% vs 31, 32%). Baseline characteristics were similar among treatment regimen groups. There was no difference in treatment selection among patients with baseline anemia or baseline neutropenia; however, doublets were preferred for those with underlying thrombocytopenia compared to triplets (93.8% vs 6.2%, p<0.01). Median first-line treatment duration was 4.1 months and did not differ among treatment groups (3.9 vs. 4.3 months; p=0.88 for doublets and triplets, respectively). At least a partial response was achieved in 47 cases (63.5%) and it did not differ between doublets and triplets (61.7% vs 66.7%). In general, first line treatment was changed in 50 (51.5%) patients and the change frequency was higher for triplets than doublets (71% vs 42.4%, p<0.01). Among patients that changed treatment, 17(34.7%) switched from a doublet to a triplet; 15 (30.6%) from a triplet to a doublet and 17 (34.7%) changed the regimen remaining as doublet or triplet, respectively. There was no difference in frequency of cytopenias, diarrhea, thrombosis or peripheral neuropathy among groups. Median event-free survival was longer in patients receiving doublet vs. triplet therapy, although the difference was not statistically significant (7.3 vs 4.3 months; p=0.06). Conclusions: We show a real-world experience of an inner city, elderly MM cohort, ineligible for autologous transplantation. A doublet combination and specifically the VD regimen was the treatment of choice in the majority of cases. In this cohort, triplet regimens did not show better response rates and led to treatment change more often than doublets. Among patients requiring treatment, approximately a third switched from doublet to triplet or viceversa which suggest that current evaluation of patient frailty at diagnosis is suboptimal. Despite similar frequency of side effects among groups, there was a trend towards longer event-free survival in patients receiving doublets. Larger retrospective studies are needed to confirm these results. Disclosures Verma: Janssen: Research Funding; BMS: Research Funding; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria.

scholarly journals Lenalidomide and Rituximab Maintenance Therapy after Front-Line Induction Chemoimmunotherapy in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5470-5470
Author(s):  
Julie E Chang ◽  
Vaishalee P. Kenkre ◽  
Christopher D. Fletcher ◽  
Aric C. Hall ◽  
Natalie Scott Callander ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Second Malignancies ◽  
Front Line ◽  
First Line ◽  
11Q Deletion ◽  
Line Chemotherapy

Introduction: Chronic lymphocytic leukemia (CLL) is incurable with standard therapy. With first-line chemotherapy, some patients (pts) may achieve durable remissions of many months/years. Lenalidomide (LEN) has improved progression-free survival (PFS) when given as maintenance (MNT) therapy after front-line chemotherapy (CALGB10404, CLLM1). The combination of LEN + rituximab (LR) has activity in relapsed CLL, hypothesizing benefit as MNT therapy after first-line chemotherapy. Methods: Adult pts ≥18 years with previously untreated CLL received induction bendamustine (B) 90 mg/m2 IV days 1 & 2 and rituximab (R) IV day 1 (375 mg/m2 cycle 1, then 500 mg/m2 cycles 2-6) for 6 treatment cycles (as few as 4 cycles allowed). MNT therapy with LR was initiated within 12 weeks after cycle 6, day 1 of BR. Criteria to start LR MNT included: neutrophils ≥1000/microliter (uL), platelets ≥75 K/uL, and creatinine clearance ≥40 mL/min. LEN was administered in 28-day cycles for 24 cycles, initially 5-10 mg daily continuous dosing, later modified to 5-10 mg on days 1-21 of each 28-day cycle in 6/2018 due to neutropenia and second malignancy risk. LEN was reduced to 5 mg every other day for toxicities at 5 mg/day. R 375 mg/m2 IV was given every odd cycle (total of 12 doses). Patients discontinuing LEN for any reason were allowed to continue R MNT per protocol. The primary endpoint is PFS with LR MNT therapy, calculated from the first day of MNT therapy until progressive disease (PD), death, or start of a new therapy. Secondary endpoints are response rate and overall survival. Results: Thirty-four pts have enrolled beginning 11/2013, with follow-up through 6/2019. Median age is 64 years, with 8 pts ≥70 years; 8 women and 26 men. CLL FISH panel is available on all pts: 14 with 13q (as sole abnormality), 9 with 11q deletion, 6 with trisomy 12, 4 with normal FISH panel and 1 with 17p deletion. Heavy chain mutation analysis is available on 11 pts: 8 unmutated, 2 mutated, 1 indeterminate. Thirty-one pts completed 4 (n=2) or 6 cycles of induction BR; 3 pts are receiving induction BR. Twenty-four pts have received MNT LR; 7 did not receive LR for reasons of PD during induction (n=2), infection (n=1), pt preference (n=2), renal insufficiency (n=1), and new carcinoma (n=1). MNT LR was completed in 7 pts; 9 pts are still receiving LR. Fourteen subjects have discontinued protocol therapy, 3 during induction due to PD (n=2) and infection (n=1), and 8 during MNT. Toxicities that led to discontinuation of LR were recurrent infections in 7 pts, including 2 events of PJP pneumonia; 4 pts had recurrent neutropenia with infections; 1 pt had neutropenia without infections. Response is assessable in 31 patients using the International Working Group Consensus Criteria. Best responses to treatment were: partial response 65% (22/34), complete response (CR)/unconfirmed CR 24% (8/34). The median number of MNT cycles received is 16. The dose intensity of LEN across total cycles received (n=278): 5 mg every other day (52.5%), 5 mg/day (43.9%), and 10 mg/day (3.6%). The most common reason for dose reduction or dose holding was neutropenia. Most common Gr 3/4 toxicities (reported as events Gr3/Gr4) during MNT therapy were: neutropenia (20/20), leukopenia (19/4), febrile neutropenia (3/1), and infections (11/-). The majority of Gr3 infections were pneumonia/respiratory (n=5). One event of disseminated herpes zoster occurred. Second malignancies during MNT included: basal cell CA (n=1), squamous cell carcinoma (n=5), and colon cancer (n=1). No unexpected second malignancies were observed in pts receiving LR. Two-year PFS (defined from day 1 of MNT therapy) is 90% (95% confidence interval [CI] 0.78-1), and the median follow-up for 24 patient who started maintenance therapy is 1.79 years (95% CI 1.53-2.7). There have been no deaths. Conclusion: The combination of LR is effective in sustaining remissions after a BR induction in previously untreated CLL, but with frequent neutropenia and infections even at low doses of LEN. Most patients discontinuing MNT did so due to neutropenia and/or infections. A shorter planned interval of MNT LR (i.e., 6-12 months) may confer similar benefit to extended dosing that is more tolerable. Pts at high risk for short remissions after front-line chemotherapy (e.g., unmutated heavy chain status, 11q deletion and/or failure to achieve minimal residual disease after induction) may be the populations for which LR MNT therapy is most appropriate. Disclosures Chang: Genentech: Research Funding; Adaptive Biotechnologies: Research Funding; Celgene: Research Funding. OffLabel Disclosure: Lenalidomide administered as maintenance therapy for first treatment of CLL/SLL.

scholarly journals Outcomes of patients with simultaneous diagnosis of chronic lymphocytic leukaemia/small lymphocytic lymphoma and multiple myeloma

2018 ◽  
Vol 185 (2) ◽  
pp. 347-350 ◽  
Author(s):  
Sikander Ailawadhi ◽  
Bhagirathbhai R. Dholaria ◽  
Sharad Khurana ◽  
Taimur Sher ◽  
Victoria Alegria ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Small Lymphocytic Lymphoma

Real-World Experience with Minimal Residual Disease Testing with Next Generation Flow Cytometry and Functional Imaging in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
David Böckle ◽  
Paula Tabares Gaviria ◽  
Xiang Zhou ◽  
Janin Messerschmidt ◽  
Lukas Scheller ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
High Risk ◽  
Functional Imaging ◽  
Real World ◽  
Research Funding ◽  
Residual Disease ◽  
Focal Lesions ◽  
High Risk Disease ◽  
Minimal Residual

Background: Minimal residual disease (MRD) diagnostics in multiple myeloma (MM) are gaining increasing importance to determine response depth beyond complete remission (CR) since novel agents have shown to induce high rates of deep clinical responses. Moreover, recent reports indicated combining functional imaging with next generation flow cytometry (NGF) could be beneficial in predicting clinical outcome. This applies in particular to the subset of patients suffering from relapsed/refractory multiple myeloma (RRMM) who tend to show a higher incidence of residual focal lesions despite serological response. Here, we report our institutions experience with implementing both functional imaging and NGF-guided MRD diagnostics in clinical practice. Methods: Our study included patients with newly diagnosed multiple myeloma (NDMM) and RRMM achieving VGPR, CR or sCR. Bone marrow aspirates were obtained for MRD-testing according to IMWG 2016 criteria. Samples were collected between July 2019 and July 2020 and analyzed with NGF (according to EuroFlowTM guidelines) at a sensitivity level of 10-5. Results were compared to functional imaging obtained with positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI). High-risk disease was defined as presence of deletion 17p, translocation (14;16) or (4;14). Results: We included 66 patients with NDMM (n=39) and RRMM (n=27) who achieved VGPR or better. In patients with RRMM the median number of treatment lines was 2 (range 2-11). Fifteen patients suffered from high-risk disease. Median age at NGF diagnostics was 64 years (range 31-83). Among patients achieving VGPR (n=27), CR (n=10) and sCR (n=29) seventeen (26%) were MRD-negative by NGF testing. CR or better was significantly associated NGF MRD-negativity (p=0.04). Notably, rates of NGF MRD-negativity were similar among patients with NDMM (28%) and RRMM (26%). Even some heavily pretreated patients who underwent ≥ 4 lines of therapy achieved MRD-negativity on NGF (2 of 9). Functional imaging was performed in 46 (70%) patients with DW-MRI (n=22) and PET (n=26). Median time between NGF and imaging assessment was 2 days (range 0-147). Combining results from imaging and NGF, 12 out of 46 (26%) patients were MRD-negative with both methods (neg/neg). Three patients displayed disease activity as measured with both, imaging and NGF (pos/pos). Twenty-nine of the remaining patients were MRD-positive only according to NGF (pos/neg), while two patients were positive on imaging only (neg/pos). More patients demonstrated combined MRD-negativity on NGF and imaging (neg/neg) in the NDMM setting than in RRMM (32% versus 19%). We also observed that 30% of the patients with high-risk genetics showed MRD-negativity on both imaging and NGF. Of note, none of the patients with very advanced disease (≥4 previous lines) was MRD-negative on both techniques. Conclusion In the clinical routine, MRD diagnostics could be used to tailor maintenance and consolidation approaches for patients achieving deep responses by traditional IMWG criteria. Our real-world experience highlights that MRD-negativity can be achieved in patients suffering from high-risk disease and also in late treatment lines, supporting its value as endpoint for clinical trials. However, our data also support MRD diagnostics to be combined with functional imaging at least in the RRMM setting to rule out residual focal lesions. Future studies using MRD for clinical decision-making are highly warranted. Disclosures Einsele: Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. Rasche:Celgene/BMS: Honoraria; GlaxoSmithKline: Honoraria; Oncopeptides: Honoraria; Skyline Dx: Research Funding; Janssen: Honoraria; Sanofi: Honoraria.

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