Named Patient Program Research Articles

Prospective cohort study evaluating efficacy and safety of efgartigimod in Chinese generalized myasthenia gravis patients.

Despite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG). This is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10 mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3 weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod's therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4 weeks. MG-ADL responder was defined as a ≥ 2-point improvement that persisted for 4 weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study. Between 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7 years, with a mean MG-ADL score of 10.86 ± 3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported. A single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients.

Real world (RW) study of patients (pts) with relapsed or refractory (RR) blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with tagraxofusp (TAG).

e18533 Background: BPDCN is characterized by clonal expansion of plasmacytoid dendritic malignant cells that express CD123 and other markers. TAG, a CD123-directed therapy, is the only drug approved to treat BPDCN (US/EU). In August 2019, a European Named Patient Program (NPP) started to ensure pt access to TAG. To assess RW safety and efficacy of TAG treatment in RR BPDCN, a pt population with a very poor prognosis, we retrospectively analyzed data from pts enrolled in the NPP. Methods: Pts with RR BPDCN received TAG 12 mcg/kg qd on days 1-5 (or by day 10) of each 21-day cycle. The first TAG cycle was given inpatient with outpatient treatment allowed thereafter. Clinicians received training on capillary leak syndrome (CLS) monitoring and management guidelines. Primary endpoints were complete response (CR) after 2-3 cycles and CLS incidence and grade (G). Secondary endpoints included number of pts bridged to stem cell transplantation (SCT), progression-free survival (PFS), overall survival (OS), best overall response rate (ORR), duration of response (DOR), and safety. Results: Of 18 pts with RR BPDCN (median age 66 y [29–83]; 89% male), 67% had received 1 prior line of therapy and 28% 2 prior lines. At initial diagnosis, pts had disease involvement in bone marrow (89%), skin (67%), and lymph nodes (61%). Median time from initial diagnosis to TAG was 7.4 mo (1–27). At a median follow-up of 8 mo, pts received a median of 2 (1–5) TAG cycles. In 15 pts with ≥1 tumor assessment, the ORR was 67% (40% CR and 27% partial response [PR]) with a median DOR of 5 mo (95% CI, 3.0–not estimable [NE]). All 18 pts had a median PFS of 4.3 mo (95% CI, 1.4–12.9) and median OS of 8.6 mo (95% CI, 3.6–NE). In 15 pts with ≥1 tumor assessment, 6 (40%) pts were bridged to SCT and had durable posttransplant responses (CR 83%; PR 17%) with median DOR, PFS, and OS not reached. CLS was mostly mild to moderate in severity; 61% of pts had CLS in cycle 1 and only 1 pt had an event in cycle 2. The median time to CLS resolution was 4 days. Other than CLS, TAG-related nonhematologic G3-4 adverse events (AEs) and serious AEs (SAEs) occurred in 44% of pts, all during cycle 1, with hepatic cytolysis, pneumonia and tumor lysis syndrome reported in 2 (11%) pts each. Grade 3-4 thrombocytopenia and pancytopenia were reported in 2 (11%) pts each. Median time to resolution was 5 days for the nonhematologic G3-4 AEs/SAEs and 18 days for thrombocytopenia. Two (11%) pts had G3-4/SAE infections. There were no treatment-related deaths. Conclusions: TAG induced fast and durable responses, and a high response rate, in RR BPDCN pts, with prolonged survival in a poor prognosis population, where historic treatments show limited efficacy. There were no new safety signals. With proper selection, monitoring, and directed intervention, CLS is manageable, usually mild, limited to the first cycle, and does not recur. These RW results support the use of TAG in pts with RR BPDCN.

Phase 2 randomized study of rintatolimod following FOLFIRINOX in patients with locally advanced pancreatic adenocarcinoma.

TPS4214 Background: The immunosuppressive microenvironment of pancreatic ductal adenocarcinoma (PDAC) is a driver of its lethality and resistance to immunotherapy. Strategies which modulate the immunosuppressive milieu have the potential to improve the anti-tumor response and improve outcomes in patients with PDAC. Rintatolimod is a synthetic double-stranded RNA molecule that activates the toll-like receptor 3 (TLR3) present on dendritic cells, B-cells, natural killer cells and pancreatic epithelial cells. TLR3 stimulation may increase cytotoxic T-cell activity in PDAC through dendritic cell maturation, antigen priming and downstream proliferation of cytotoxic T-cells. Twenty-seven patients were treated with rintatolimod in a single center Named Patient Program at Erasmus University Medical Center in Rotterdam between January 2017 and February 2019. All had locally advanced or metastatic PDAC which had not progressed on FOLFIRINOX (median 8 cycles). Maintenance rintatolimod, administered intravenously twice weekly for up to 18 weeks, was generally well tolerated. The most common toxicities were grade 1-2 myalgia (30%), chills (52%) and fatigue (30%); no toxicities ≥ grade 3 were observed. Progression-free and overall survival (from cycle 1 FOLFIRINOX) were 13 and 19 months. Methods: This is a phase 2 randomized, open-label, multicenter clinical trial. The primary objective is to assess the efficacy of rintatolimod compared to observation in subjects with locally advanced PDAC which has not progressed after FOLFIRINOX. Eligible patients have completed at least 4 months of FOLFIRINOX, have no evidence of progressive disease, have measurable disease by RECIST v1.1, Karnofsky Performance Status ≥80 and have adequate organ function. Subjects with resected PDAC or metastatic disease are not eligible. Subjects are randomized 2:1 to rintatolimod vs. observation. Rintatolimod is administered intravenously twice weekly until disease progression in the experimental arm. Cross-sectional imaging is performed every 8 weeks in both arms. The primary endpoint is progression-free survival, as assessed by the investigator. Secondary endpoints include overall survival, objective response rate, duration of response and safety, as assessed by CTCAE v5.0. Exploratory endpoints include quality of life and changes in immune cell composition and T-cell response in the peripheral blood to characterize the immunomodulatory effects of rintatolimod. The planned sample size is 90 subjects. The final analysis will be performed after 64 events (disease progression or death) have been observed. The study is powered to detect a hazard ratio of 0.47 for median PFS with 80% power and significance level of 5%. Clinical trial information: NCT05494697 .

Abstract PO3-16-12: European real-world experience of patients with HER2+ advanced/metastatic breast cancer accessing trastuzumab deruxtecan through a named patient program: first interim analysis of EUROPA T-DXd

Abstract Background: In 2021, trastuzumab deruxtecan (T-DXd) monotherapy was conditionally approved in the EU for adult patients with human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic breast cancer (mBC). A named patient program (NPP) was initiated (March 2021) to enable eligible patients with an unmet medical need to gain access to T-DXd when not yet available locally, either commercially or through an appropriate clinical trial. Centers that treated/are treating patients under this NPP were invited to participate in EUROPA T-DXd real-world data (RWD) collection. Methods: EUROPA T-DXd is an ongoing, multicenter (Ireland, Italy, and Spain), observational (retro- and prospective) study of RWD from approximately 200 adult patients with HER2+ advanced/mBC who had received ≥2 prior anti-HER2 regimens and for whom T-DXd was initiated through the NPP. Collection of RWD is optional and independent of eligibility for the NPP. The primary objective is to estimate real-world time to treatment discontinuation (rwTTD). Secondary objectives include real-world progression-free survival (rwPFS), reasons for T-DXd discontinuation, safety, and prior anti-HER2 treatment patterns. Results: This first interim analysis included 84 evaluable patients. Patients had a mean (standard deviation) age of 53.4 (11.1) years; most were female (97.6%) and had HER2 immunohistochemistry 3+ (70.2%), and 44% had received >3 prior lines of anti-HER2 therapy in the metastatic setting (Table). At data cutoff (June 5, 2023), 50 (59.5%) patients were still receiving T-DXd. In total, 34 patients (40.5%) discontinued T-DXd (death, n=1 [1.2%]; adverse event, n=3 [3.6%]; disease progression, n=26 [31%]; or other, n=4 [4.8%]). Median rwTTD was 21.4 months (95% confidence interval 17.6, not estimated), and median rwPFS was not reached. The results of the wider cohort will be presented at the meeting, including adverse events. Conclusion: Results from this first interim analysis confirm the efficacy of T-DXd in heavily pretreated patients with HER2+ mBC. Baseline characteristics and demographics are comparable to the clinical trial setting. Analyses are ongoing and will provide more mature rwTTD and rwPFS. XX XX Citation Format: Michelino De Laurentiis, José Ángel García-Sáenz, Giampaolo Bianchini, Cristina Saura, Hans Wildiers, Arthur Allignol, Amanda Logue, Markus Lucerna, Sabine Stamenitis. European real-world experience of patients with HER2+ advanced/metastatic breast cancer accessing trastuzumab deruxtecan through a named patient program: first interim analysis of EUROPA T-DXd [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-16-12.

Belantamab mafodotin in triple-refractory multiple myeloma patients: A retro-prospective observational study in Italy.

Belantamab mafodotin is the first-in-class antibody-drug conjugates targeting B-cell maturation antigen to have demonstrated effectiveness in triple-class refractory multiple myeloma (TCR-MM) patients. We performed a retrospective study including 78 TCR patients, with at least four prior lines of therapy (LOTs), who received belantamab mafodotin within named patient program and expanded access program in Italy between 2020 and 2022. Median age was 65 years (range 42-86 years), ECOG performance status was ≥1 in 45% of patients. Overall, a clinical benefit was obtained in 36 out of 74 evaluable patients (49%), with 43%, 28%, and 13.5% achieving at least partial response, very good partial response, and complete response, respectively. After a median follow-up of 12 months (range 6-21 months), median duration of response, progression-free survival (PFS), and overall survival (OS) were 14, 5.5, and 12 months, respectively. Age >70 years, good performance status and response were associated with longer PFS and OS. Keratopathy occurred in 58% of patients (G3 2.5%), corneal symptoms in 32% (G3 1.2%) and a reduction in visual acuity in 14%. Grade 3 thrombocytopenia occurred in 9% of patients. Only 3% of patients discontinued belantamab mafodotin because of side effects. This real-life study demonstrated significant and durable responses of belantamab in TCR-MM patients with four prior LOTs, otherwise ineligible for novel immunotherapies.

Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34+ cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34+ cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34+ cells infused and younger age at GT affected positively the plateau of CD3+ transduced cells, lymphocytes and CD4+ CD45RA+ naive T cells, whereas the cell dose positively influenced the final plateau of CD15+ transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT03478670 .

Comparison of Lenalidomide Based Triplets (IRD, KRD and DRD) in Relapsed and Refractory Multiple Myeloma in Routine Practice

Background: Treatment of relapsed and refractory multiple myeloma (RRMM) has become a chalenge with the introduction of combined lenalidomide-based triplets. The addition of proteasome inhibitors (PI) or monoclonal antibodies (MoAb) significantly improved the therapeutic outcomes of previous RD regimen (lenalidomide, dexamethasone). The clinical trials with RD triplets confirmed the outstanding synergistic effects of lenalidomide with PIs or MoAbs. However, the outcomes between individual regimens are not easily comparable as the trials used different cohorts of patients. Moreover, the clinical trials often overestimate the outcomes due to selection bias. Aims: Our aim was to compare the outcomes of lenalidomide-based triplets in an unselected “real-world population”. Patients and methods: We performed a large registry based analysis of RRMM patients treated with daratumumab, lenalidomide and dexamethasone (DRD), carfilzomib, lenalidomide and dexamethasone (KRD), and ixazomib, lenalidomide and dexamethasone (IRD) from the Czech Registry of Monoclonal Gammopathies (RMG) treated within 1st-3rd relapse. We excluded patients treated in clinical trials as well as patients with follow-up shorter than 6 months. For the IRD combination we performed 2 separate analyses: from 2016-2018 (early IRD, e-IRD) and 2019 onwards (late IRD, l-IRD), as the first cohort was treated within a Named Patient Program and had no competitive RD triplet or clinical trial, whereas patients treated after 2019 were those who were generally not eligible for competing KRD or DRD regimens. Altogether we assessed 224 patients with DRD regimen, 143 with KRD, 104 with e-IRD and 67 with l-IRD regimen. Data were described by absolute and relative frequencies of categorical variables and median (min-max and 5 th-95 th percentile) for quantitative variables. Survival analysis for different endpoints - overall survival (OS), progression free survival (PFS), time to next treatment (TNT), and duration of therapy (DOT) - was conducted using the Kaplan-Meier method complemented by the 95% Greenwood confidence interval for estimates of probability survival. Statistical significance of differences in survival among subgroups was assessed using the log-rank test. All statistical tests were performed at a significance level of α = 0.05 (all tests two-sided). Results: There were slight but significant differences within the demographic data: Patients treated with DRD and KRD were younger than patients on both e-IRD and l-IRD (median 65.5 vs 64.4 vs 67.2 vs 69.9 years) and had better overal performance status (PS 0 or 1 in 87.9 vs 92.2 vs 83.5 vs 76.1%). They were also less pretreated (1 previous line in 73.2 vs 70.6 vs 62.5 vs 38.8%). Also, patients on DRD and KRD had slightly lower ISS stage versus e-IRD and l-IRD patients (ISS 1 in 48.4 vs 55.5 vs 42.2 vs 37.5%). Patients on KRD had slightly higher presence of extramedullary and/or paraskeletal disease (45.6% versus 32.5% and 35.0% vs 31.6% in DRD and e-IRD and l-IRD, respectively). The presence of high-risk cytogenetics was higher in KRD and l-IRD (42.7 vs 53.1%) than in the e-IRD and DRD group (32.3% and 24.6%). The overal response rates (ORR) in DRD, KRD, e-IRD and l-IRD were following: 91.4% vs 89.6% vs 79.6% vs 70.8%. The rates of very good partial response or better (VGPR+) were 67.3% vs 62.3% vs 40.8% vs 25%. Median PFS in DRD vs KRD vs e-IRD vs l-IRD was 23.64 vs 16.52 vs 19.97 vs 11.57 months. Due to short follow-up, the median OS was not assessable with an estimate around 40 months for all the cohorts. The toxicity was similar to the data reported from clinical trials with no new safety alerts. Conclusions: We conclude that lenalidomide based triplets (DRD, KRD and IRD) have significant efficacy in RRMM even in the routine clinical practice but as expected, they do not achieve the outcomes reported in clinical trials. DRD regimen seems to be the most efficient regimen even in “real-world” setting but the results are biased by the cohort heterogeneity. The outcome of a regimen in “real-world” depends significantly on other variables including competing regimens or clinical trials, and may have large individual differences as seen in the case of e-IRD (assessed at the time with no competing lenalidomide-based triplets) versus l-IRD (influenced by the choice between several effective modalities). Supported by MH CZ - DRO (FNOL, 00098892).

Treatment Patterns and Outcomes in Patients with Multiple Myeloma Who Received Ixazomib and in Patients with Triple-Class Refractory Multiple Myeloma: A Retrospective, Observational, Real-World Historical Database Analysis Study from China

Background: Multiple myeloma (MM) is a fatal, malignant disease of plasma cells characterized by an abnormal proliferation of monoclonal antibodies. China is estimated to have 22,450 newly diagnosed (ND) cases of MM and 17,360 related deaths in 2022. Emerging novel therapies have significantly improved survival in MM, and treatment guidelines have been updated to reflect these advances. Ninlaro® (ixazomib) is the first oral proteasome inhibitor (PI) approved by the US FDA in 2015 and by China's National Medical Products Administration in 2018 (conditionally) for MM patients receiving ≥1 prior therapy owing to its convincing efficacy and well-tolerated safety profile as seen in the landmark Phase III TOURMALINE-MM1 trial and the China Continuation Study. Novel drugs such as PIs, immunomodulatory drugs (IMDs), and anti-CD-38 monoclonal antibodies are the core component of MM treatment and have improved patient outcomes considerably. However, many patients remain refractory to these drugs (triple-class refractory, TCR) and have poor clinical outcomes. There is a lack of real-world evidence characterizing treatment patterns and outcomes of MM patients receiving ixazomib and TCR-MM patients, in China. The objective of this study is to bridge this data gap by providing vital information on the treatment patterns and outcomes, and healthcare resource utilization in Chinese MM patients receiving ixazomib and TCR-MM patients in real-world clinical practice. Study Design and Methods: This study is an ongoing, single-centre, non-interventional, retrospective database analysis study of MM patients identified from the Chinese National Longitudinal Cohort of Haematologic Diseases (NICHE)-MM registry, a historical and ongoing longitudinal data registry of the Institute of Haematology and Blood Diseases Hospital (IHBDH), and representing the top-tier MM care in China. The patients will be divided into two groups. Patients (aged ≥18 years) with a confirmed MM diagnosis receiving all ixazomib-based regimen as 2nd-line and above therapy (RR-MM), or as a 1st-line therapy (ND-MM) will form group one and TCR-MM patients' refractory to at least one IMiD (lenalidomide, pomalidomide or thalidomide), one PI (bortezomib, ixazomib, or carfilzomib) and one anti-CD-38 monoclonal antibody (daratumumab and isatuximab) will form group two. TCR-MM patients receiving ixazomib will be part of both groups. Patients enrolled in clinical trials will be excluded. The data for analysis will be collected from the ixazomib launch date in China (April 12, 2018) and/or the index date of the first patient enrolled in ixazomib Named Patient Program to September 2023 (tentative). Since 2000 till January 2023, the NICHE-MM registry has enrolled 3,329 MM patients of whom 156 patients have received ixazomib. This is the preliminary sample count and the final sample size will be calculated during data cleaning and analysis phases. The primary objective of this study will be to determine 1) treatment patterns and responses by lines of treatments and 2) time-to-event outcomes. The treatment patterns will include treatment name, dosage, type (induction, consolidation, or maintenance), number of cycles, duration and severe adverse event causing hospitalization. The treatment responses will include complete response (CR), stringent CR, partial response (PR), very good PR, minimal response, stable disease, and progressive disease as defined by the International Myeloma Working Group. The overall response rate of the last line of treatment for both study groups will be calculated as composite endpoint. Time-to-event outcomes will include progression-free survival, overall survival, duration of therapy, and time to next line of treatment in ND/RR-MM and TCR-MM patient groups. Secondary objectives will include assessment of patients' demographic, disease and clinical characteristics. Depending on data availability, the exploratory objective will be to determine the healthcare resource utilization and costs incurred by patients in both groups. Subgroup analysis between ND-MM vs. RR-MM or RR-MM patients receiving ixazomib in 2nd-line setting vs. TCR-MM patients receiving ixazomib in >3rd-line setting is also planned. Descriptive statistics will be used for the analyses. Our findings will also help clinicians in making strategic decision about more apt positioning of ixazomib in the treatment algorithm of MM.

Durable Outcomes with Manageable Safety Leading to Prolonged Survival with Tagraxofusp for Treatment-Naive Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm: Updated Results from a European Named Patient Program

Introduction:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive orphan hematologic malignancy that mostly presents in skin, bone marrow, and blood. BPDCN is characterized by clonal expansion of plasmacytoid dendritic tumor cells that express specific markers, including CD123. Historically, median overall survival (OS) has been ~8-14 months (mos) following chemotherapy, and the only potential cures can be conferred by hematopoietic stem cell transplantation (HSCT) following successful induction. Tagraxofusp (TAG) is a first-in-class CD123-directed therapy and the only drug approved in the US and EU to treat BPDCN. In August 2019, a global Named Patient Program (NPP) was initiated in Europe to increase patient (pt) access to TAG. We present updated results, including over two years of follow-up, in treatment-naïve pts with BPDCN from the NPP to assess TAG safety and efficacy in the real-world setting. Methods:A European multi-center, non-interventional, retrospective study was conducted in adult BPDCN pts that had access to TAG via the NPP. The main inclusion criterion was a diagnosis of BPDCN. Intravenous TAG as first-line therapy was given at 12 mcg/kg once daily on days 1-5 (up to day 10 allowed) of a 21-day cycle. Hospitalization was required for the first cycle only; subsequent cycles could be administered in an outpatient setting. Training of physicians, nurses, and pharmacists on clinical management guidelines was mandatory before initiation of treatment.The main endpoints were complete response (CR) rates and incidence and grade (G) of capillary leak syndrome (CLS). Secondary outcomes included the number of pts bridged to HSCT, OS, and safety. Results: Twenty-two treatment-naïve adult pts were enrolled in the European NPP from 08/2019 to 12/2021. Median age was 68 yrs (21 - 82), and 86% were male. Sites of disease involvement at diagnosis included skin 77%, bone marrow 59%, lymph nodes 55% (9% single; 46% multiple), and spleen 36%; 10% had CNS involvement at baseline. Median time from diagnosis to initiating TAG was 1.5 mos (range, 0.4 - 9), and the median number of TAG cycles was 3 (1 - 8). At a median follow-up of 10 mos (0.2 - 25), 18 pts had at least 1 tumor assessment. The overall response rate (ORR) was 89% (95% CI, 65 - 99), including a CR rate of 67% (95% CI, 41 - 87) and a partial response (PR) rate of 22%. Median time to ORR was 21 days (11 - 74), and median time to CR was 29 days (11 - 58). Allogeneic HSCT was undertaken in 11/22 (50%) pts; of these 7 (64%) pts were in CR prior to HSCT, and 4 (36%) pts were in PR. Of the 2 pts with CNS involvement at baseline, both had CNS clearance by intrathecal chemotherapy (IC), achieved a CR in response to TAG, and were transplanted. Median OS for all pts was 20 mos (95% CI, 10 - not reached [NR]), Figure. Median OS was NR in transplanted pts (n = 11) and was 11 mos in non-transplanted pts (n=11; 95% CI, 0.2 - NR). Median duration of response (ie, time from CR/CRi to progression or death) was 8.9 mos (95% CI, 2.2 - NR). The majority of G3/4 adverse events (AEs) or serious AEs, regardless of their relationship to TAG therapy, occurred during cycle 1. Thrombocytopenia was the most frequent hematological G3/4 AE occurring in 7 pts (32%), followed by neutropenia (18%). Overall, CLS events were observed in 10 pts (ie, edema [n=9], weight gain [n=8], hypotension [n=5], and/or hypoalbuminemia [n=1]). Nine events occurred in cycle 1, and 3 pts experienced a second CLS event. The majority of CLS events were mild to moderate (69% G≤2; 31% G3). There were no G4/5 events. Most CLS events were managed with albumin supplementation (92%) and temporary changes in TAG scheduling (69%). Median duration of CLS was 8 days, and all events resolved. No patient with CNS involvement had a CLS event. As of the data cut-off, 2 pts (9%) remain on treatment with TAG. Conclusion: Pts with treatment-naïve BPDCN who received TAG achieved durable outcomes with prolonged survival, including those with known CNS involvement. With over 2 yrs of follow-up, median OS was 20 mos with TAG, which compares favorably to chemotherapy's shorter median OS of ~8-14 mos. No new safety signals were observed. CLS was manageable; the majority of events occurred in cycle 1 and were mild/moderate, with no G4/5 events. These real-world results from a European NPP are consistent with the long-term safety and efficacy results demonstrated in the pivotal TAG monotherapy study (Pemmaraju JCO 2022) and further support TAG treatment for pts with BPDCN.

5613294 BASELINE PATIENT CHARACTERISTICS FROM A UK EARLY ACCESS TO MEDICINES SCHEME (EAMS) WITH VOXELOTOR, A HBS POLYMERIZATION INHIBITOR, FOR THE TREATMENT OF HEMOLYTIC ANEMIA DUE TO SICKLE CELL DISEASE

Background: Standard of care for patients with sickle cell disease (SCD) typically includes blood transfusions and treatment with hydroxyurea (HU). Voxelotor, a first-in-class oral treatment, inhibits sickle hemoglobin polymerization, the molecular basis of red blood cell sickling. Voxelotor is approved in the United States for the treatment of SCD in patients aged ≥4 years and in the European Union, Great Britain, United Arab Emirates, Kuwait, and Oman for patients aged ≥12 years. Voxelotor has been provided to eligible patients with SCD in the United Kingdom (UK) through a Medicines and Healthcare Products Regulatory Agency – approved Early Access to Medicines Scheme (EAMS) and through a company Named Patient Program (NPP), both of which allow patients to receive new, unlicensed medicines when there is a clear unmet need. Aims: To describe the UK patient population participating in the voxelotor EAMS and NPP for the treatment of hemolytic anemia due to SCD. Methods: Patients aged ≥12 years with hemoglobin (Hb) ≤10.5 g/dL received voxelotor. The EAMS permitted patients to receive a stable dose of HU for 3 months prior to starting voxelotor, whereas NPP allowed patients who were ineligible or intolerant to HU, had a poor/no response to HU, or had stopped taking HU. Data on demographics, comorbidities, concomitant medications (including blood transfusions), adverse events, markers of hemolysis, vaso-occlusive crises (VOCs) requiring treatment and/or hospitalization, and discontinuation of therapy were collected. Results: As of August 22, 2022, 90 patients (61 in the EAMS and 29 in the NPP) were enrolled. Overall, the mean age (range) was 37.82 years (12-66), 53.33% (48/90) were female, 75.56% (68/90) were of African or Afro-Caribbean origin, and the most common genotype was HbSS (97.78%, 88/90) (Table). At baseline, mean (SD) [range] Hb was 7.54 (1.43) [4.6-10.8] g/dL. At baseline, 45.9% (28/61) of patients were taking HU, and 18.03% (11/61) had discontinued previous use of HU; 1.64% (1/61) had been treated with crizanlizumab, and 50.82% (31/61) reported having simple and/or exchange transfusions. In the 12 months before initiating voxelotor, the mean (SD) number of VOCs requiring hospitalization was 0.84 (1.52). Other reasons for hospitalization included admission for VOC (24.59%, 15/61), acute chest syndrome (4.92%, 3/61), transfusion (9.84%, 6/61), hyperhemolysis (3.28%, 2/61), and other (9.84%, 6/61). A total of 9.84% (6/61) of patients reported ≥3 emergency department (ED) admissions, and alloimmunization was reported in 19.67% (12/61) of patients. Summary/Conclusion: The UK EAMS and NPP provide voxelotor to patients with SCD with limited treatment options. Clinical measures, ED visits, and hospital admission rates of patients participating in the voxelotor EAMS and NPP demonstrate the characteristics of patients selected for the early access scheme and highlight the unmet treatment needs among representative patients with SCD in the UK. Baseline hemolytic parameters and Hb levels are critical not only for defining patient eligibility, but as follow-up measures for patients while receiving voxelotor treatment. Data on the impact of voxelotor on clinical outcomes are forthcoming. Funding: This study was supported by Global Blood Therapeutics.Reference 1. Medicines and Healthcare Products Regulatory Agency. Voxelotor: treatment protocol: information on the pharmacovigilance system. Updated August 5, 2022. Accessed August 28, 2022. https://www.gov.uk/government/publications/voxelotor-in-the-treatment-of-sickle-cell-disease/voxelotor-treatment-protocol-information-on-the-pharmacovigilance-system

Real-world experience of Australian and New Zealand patients with chronic lymphocytic leukemia and mantle cell lymphoma accessing ibrutinib through a Named Patient Program

Ibrutinib is a small molecule inhibitor of Bruton’s tyrosine kinase indicated for the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). The Named Patient Program in Australia and New Zealand (ANZ NPP) provided access to ibrutinib treatment to 1126 R/R CLL/SLL and 330 R/R MCL patients, prior to Pharmaceutical Benefits Scheme listing. This study aimed to assess the duration of treatment for the ANZ NPP patients, as an indicator of efficacy and tolerability of ibrutinib in the real world. Based on the NPP data, ibrutinib provided a median of 47 months clinical benefit for participants with CLL/SLL and 14 months clinical benefit for those with MCL; outcomes that are consistent with the clinical trial results and further support the well-established efficacy and safety profile of ibrutinib in the real world.

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy.

After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy.

Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey.

Polatuzumab vedotin (Pola) with bendamustine and rituximab (BR) is a promising option for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We analyzed the data of 71 R/R DLBCL patients who had been treated with Pola-BR in the named patient program from March 2018 to April 2021 from 32 centers in Turkey. All patients received up to six cycles of Pola 1.8mg/kg, rituximab 375mg/m2 on day 1, and bendamustine 90mg/m2 on days 1-2 of each cycle. Median age at Pola-BR initiation was 55 (19-84). The overall response rate was 47.9%, including 32.4% CR rate when a median of 3 cycles was applied. With a median follow-up of 5months, the median OS was 5months. Grade 3-4 neutropenia and thrombocytopenia were the most common hematological toxicities. The real-world data from our cohort showed the Pola-BR is an effective option with a manageable toxicity profile.

Belantamab Mafodotin in Patients with Relapsed and Refractory Multiple Myeloma Who Have Received at Least One Proteasome Inhibitor, One Immunomodulatory Agent and One Anti-CD38 Monoclonal Antibody: A Retro-Prospective Italian Observational Study

Despite a significant improved outcome in Multiple Myeloma (MM) patients due to introduction of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs), occurrence of resistance to these agents results in a poor survival with the need for effective therapies in this setting. Belantamab mafodotin (belamaf) represents the first-in-class antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA) to be approved for treatment of relapsed/refractory MM (rrMM) patients who have previously received at least four lines of therapy after it demonstrated meaningful activity as monotherapy in the phase II DREAMM-2 study. Real-world data of belamaf use is scarce since the number of patients in the study cohorts are low. We carried out a retro-prospective study aiming to evaluate efficacy and safety of belamaf monotherapy in RRMM patients treated according to compassionate use programmes as Named Patient Program (NPP) and Expanded Access Program (EAP) in 60 Italian centers under the aegis of European Myeloma Network (EMN). The primary endpoint of this study was the rate of patients achieving a clinical benefit (at least minimal response according to IMWG criteria). Secondary endpoints were ORR (at least PR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS). Eligible patients must be ≥18 years of age with a MM diagnosis according to IMWG criteria; they must have received at least 4 previous therapies and be refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody. Moreover, patients had to have an ECOG performance status ≤ 2 and adequate organs function. Overall, 182 patients have been treated with belamaf within the compassionate use programmes, 138 in the NPP program and 44 in the EAP program. In July 2022, 23 patients are still receiving therapy with belamaf (7 are from NPP program). Notably, 2 patients have received 9 belamaf cycles, 8 patients received more than 11 cycles, 8 patients more than 15 cycles and 5 patients at least 20 cycles. Moreover, one patient was given 34 cycles and another 36 ones. This is the largest real-life study on belamaf monotherapy in rrMM. Data on efficacy and safety will be detailed at the meeting.

1683P Implementing next generation sequencing (NGS)/molecular tumor board (MTB)-based precision oncology practice: One-year experience at the Verona University Hospital

Cancer is a multifactorial genetic disease: NGS-based broad genomic profiling allows the identification of potential molecular drivers. Evaluation of the clinical actionability of NGS results should be guided by the expert consensus of a MTB, providing management recommendations and translating molecular alterations into clinical indications. Here we describe the MTB experience at the Verona University Hospital. Between Feb 2021 and Mar 2022, 315 patients (pts) with advanced solid malignancies deemed orphan with respect to established molecular diagnostics and availability of standard molecularly targeted treatments, had access to somatic profiling using targeted NGS panels. NGS results were discussed at bi-weekly MTB meetings, encompassing oncologists, pathologists, geneticists, pharmacologists, and pharmacists. The three most represented primary tumors were pancreatic (30%), breast (16%) and head and neck (14%) cancers. Among 315 pts profiled (13% of the annual active oncological population at our Center), 42 were discussed at MTB meetings, so far: 15 patients (36%) received a treatment recommendation: 4 within an ongoing clinical trial, 11 through atypical drug access (authorized off label use, named patient programs and other access schemes). Six pts (14%) were referred for genetic counseling, based on evidence of potential germline alterations at somatic testing. Further molecular investigations were requested/proposed in 11 pts (26%): IHC in 5, germline testing in 5, and a second NGS test + IHC in 1 pt, respectively. NGS-based profiling is a comprehensive tool to identify potentially actionable targets in advanced solid tumors. Its systematic application may have a profound impact on individual pts clinical course and outcomes. MTB discussion successfully provided suitable management strategies in a significant fraction of pts. Based on the careful definition of the criteria for accessing NGS profiling and the consequent MTB discussion, such approach should become a constitutive part of the oncological care program in the era of precision medicine.

Old and New Drugs for Chronic Lymphocytic Leukemia: Lights and Shadows of Real-World Evidence.

Several novel treatments for chronic lymphocytic leukemia (CLL) have been recently approved based on the results of randomized clinical trials. However, real-world evidence (RWE) is also requested before and after drug authorization in order to confirm safety and to provide data for health technology assessments. We conducted a scoping review of the available RWE for targeted treatments of CLL, namely ibrutinib, acalabrutinib, idelalisib, and venetoclax, as well as for chemoimmunotherapy (CIT). In particular, we searched studies published since 1 January 2010 and reported outcomes of the above treatments based on health databases, registries, or phase IV studies, including named-patient programs. We included both full papers and abstracts of studies presented at major meetings. Overall, 110 studies were selected and analyzed: 28,880 patients were treated with ibrutinib, 1424 with idelalisib, 751 with venetoclax, 496 with acalabrutinib, and 14,896 with CIT. Reported discontinuation rates were higher than in clinical trials, while effectiveness could not be indirectly compared with clinical trials since a detailed case mix, including cytogenetic risk factors, was partially available and propensity scores rarely applied. RWE on CLL can help to set realistic outcomes with novel treatments, however, real-world studies should be fostered, and available data shared.

Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program.

Simple SummarySurvival of patients with locally advanced and metastatic pancreatic cancer remains poor after standard care with FOLFIRINOX. It is not known whether treatment with rintatolimod, a TLR-3 agonist, would improve progression-free survival. We investigated the immunomodulatory effects of rintatolimod and its benefits regarding progression-free and overall survival in patients who had been pre-treated with FOLFIRINOX. In long-term survivors (11 patients), we observed that rintatolimod treatment resulted in a lowering of the systemic immune-inflammation index (SIII) as well as the neutrophil to lymphocyte ratio (NLR), whereas peripheral B-cell counts were higher, when compared to short-term survivors (16 patients). Of note, rintatolimod treatment was associated with a higher progression-free and overall survival when compared to matched controls. These results support the effectiveness of adding rintatolimod as a maintenance therapy after FOLFIRINOX treatment in patients with advanced pancreatic cancer. A randomized controlled trial to further determine the efficacy of the drug is recommended.Background: Treatment with the TLR-3 agonist rintatolimod may improve pancreatic cancer patients’ survival via immunomodulation, but the effect is unproven. Methods: In this single-center named patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with rintatolimod (six weeks total, twice per week, with a maximum of 400 mg per infusion). The primary endpoints were the systemic immune-inflammation index (SIII), the neutrophil to lymphocyte ratio (NLR), and the absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Subgroup analyses were performed in long-term survivors (>1-year overall survival after starting rintatolimod) and compared to short-term survivors (≤1 year). Results: Between January 2017 and February 2019, twenty-seven patients with stable LAPC or metastatic disease were pre-treated with FOLFIRINOX and treated with rintatolimod. Rintatolimod treatment was well-tolerated. The SIII and NLR values were significantly lower in the 11 long-term survivors, versus 16 short-term survivors. The numbers of B-cells were significantly increased in long-term survivors. Numbers of T cells and myeloid cells were not significantly increased after treatment with rintatolimod. Median PFS was 13 months with rintatolimod, versus 8.6 months in a subset of matched controls (n = 27, hazard ratio = 0.52, 95% CI = 0.28–0.90, p = 0.007). The median OS was 19 months with rintatolimod, versus 12.5 months in the matched control (hazard ratio = 0.51, 95% CI = 0.28–0.90, p = 0.016). Conclusions: Treatment with rintatolimod showed a favorable effect on the numbers of peripheral B cells in patients with pancreatic cancer and improved survival in pancreatic cancer, but additional evidence is required.

Luspatercept in MDS with Ring Sideroblasts: A Real-Life Multicenter Experience from a Named Patient Program

BackgroundLow risk Myelodysplastic syndromes (LR MDS) are a heterogeneous group of clonal disorders of the hematopoietic stem cell characterized by ineffective hematopoiesis, peripheral cytopenias and relative increase of bone marrow blasts [List 2004]. The most common cytopenia is anemia, which occurs in 85-90% of cases (isolated in 35% of cases) [Fenaux 2013], and ranges from mild/asymptomatic to transfusion dependent. The standard of care for anemia remains supportive care and about 70% of cases benefits from erythropoiesis-stimulating agents (ESAs).According to the FAB classification, a low-risk group of MDS characterized by the presence of ring sideroblasts (RS) was recognized. In the 2017 WHO classification, the nosologic entities of MDS uni-linear and multi-linear dysplasia with RS (MDS-UD-RS, MDS-MD-RS) were established, to emphasize the importance of identifying forms with a potential therapeutic target [Arber 2016].Luspatercept is a recombinant fusion protein consisting of the modified extracellular domain of human activin receptor type IIB (ActRIIB) linked to a domain of human immunoglobulin Fc G1. The drug showed efficacy in re-establishing erythropoiesis and was recently approved for the treatment of adult patients with very low- to intermediate-risk MDS-RS failing ESAs[Platzbecker 2017; Fenaux 2020].AimsTo retrospectively assess the efficacy and/or clinical benefit (defined as a reduction in red blood cells transfusions [RBCT] or increase in hemoglobin levels) of luspatercept in patients with LR MDS with RS in a real-life setting. Safety issues were also addressed and clinical and hematological predictors of outcome analyzed.MethodsWe considered all IPSS-R lower-risk MDS with RS patients with unsatisfactory response or unsuitable for ESAs, treated with luspatercept as monotherapy through an expanded access program since November 2020, in 2 tertiary hematologic centers in Milan, Italy. Luspatercept was administered according to the published schedule: starting dose 1,0 mg/kg every three weeks, with the possibility to increase up to 1,33 mg/kg and 1,75 mg/kg if patients did not reach transfusion independence or decreased transfusion burden after two consecutive infusions. Response to luspatercept was evaluated according to IWG 2018 criteria: Hb increase by > 1.5 g/dL and/or relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk.ResultsWe included a total of 17 pts (70% males, 30% females), with a median age of 68 years (range 45-89). The median follow-up from the start of the Luspatercept was 4 months (range 3-6).According to WHO 2017 we included 13 MLD (76%) and 4 ULD (24%); in all of them SF3B1 mutations was confirmed. Moreover, According to IPSS-R classification: 5 (27%)cases were intermediate and 12 (73%) low risk.All patients received at least three doses of luspatercept. Nine patients (53%) needed a dose escalation to 1,33 mg/kg, and 7 (41%) required the maximal dose of 1,75 mg/kg. Interestingly, not all patients received a dose escalation, and 8 (47%) obtained prolonged efficacy with 1 mg/kg dose.Hemoglobin levels increased in 9 pts (53%): 4 (24%), 3 (18%) and 2 (12%) cases at 1 mg/Kg, 1,33 mg/kg and 1,75 mg/dl, respectively. Medina increase was 1,5 g/dl (range 0,2 - 2,2) and these levels were maintained for a median of 4 months (range 3-6).In addition, considering transfusion burden, the independence was reached in 3 pts (18%), after a median time of 6 weeks from treatment start. Importantly, off the 14 patients remaining transfusion-dependent, 6 (35%) reduced the transfusion burden.The most prominent toxicity was increased blood pressure (grade 2) occurring in 3 pts (18%), and dizziness (grade 2) in 2 pts (12%); though the drug was generally well tolerated. No serious adverse events (SAEs) were reported. Therefore, patients were treated as outpatients in all cases.At the last follow up, all patients are alive and free from leukemic evolution.Conclusions:Our real-world experience confirms the efficacy of luspatercept in improving erythropoiesis and decreasing transfusion dependency in very low, low or intermediate risk MDS with RS, with an acceptable toxicity profile. DisclosuresFattizzo: Amgen: Honoraria, Speakers Bureau; Apellis: Speakers Bureau; Annexon: Consultancy; Momenta: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Alexion: Speakers Bureau; Kira: Speakers Bureau. Barcellini: Agios: Honoraria, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Honoraria; Novartis: Honoraria.

Ixazomib, lenalidomide, and dexamethasone combination in "real-world" clinical practice in patients with relapsed/refractory multiple myeloma.

Ixazomib is approved for use in combination with lenalidomide and dexamethasone (IRd) for patients with multiple myeloma (MM) who received at least one previous therapy. Registration study "TOURMALINE MM-1" was published in 2016. Nevertheless, clinical trials are significantly different from real-world use. From June 2016 to December 2018, IRd was available for Slovak patients with relapsed/refractory MM through a Named Patient Program. The aim of this study was to evaluate the efficacy and safety of ixazomib. We analyzed in this cohort study outcomes of 106 MM patients treated with IRd at 2 academic centers. The median age at diagnosis was 63years (44-78). The median number of prior lines was 2 (1-7). The majority had high international staging system (ISS) score: 18, 29, and 59 were in the ISS I, ISS II, and ISS III groups, respectively. Treatment continued until progression, unacceptable toxicity, or death. The median follow-up for the entire cohort was 29 (0-49) months. The overall response rate was 74.5% (complete remission, 7.5%; partial remission, 67%). The median overall survival was not reached. Median progression-free survival (PFS) was 43months (95% CI 35.6-50.4). The Kaplan-Meier method was used to generate survival curves, and we compared the influence of different factors on PFS. The most common hematological adverse events of any grade were neutropenia (90.4%), anemia (55.6%), and thrombocytopenia (43.4%). Our real-world data support the use of IRd as a highly effective and well-tolerated oral treatment protocol for relapsed myeloma.

Long-time progression-free survival in relapsed, refractory multiple myeloma with the oral ixazomib-lenalidomide-dexamethasone regime

Despite great advances in therapy, multiple myeloma is still a largely incurable disease, therefore the importance of salvage therapies is paramount. The first oral proteasome inhibitor ixazomib in combination with lenalidomide-dexamethasone is a tolerable, orally administered regime, which has become available for Hungarian relapsed, refractory multiple myeloma patients from April 2015 in the Named Patient Program. Our goal was to investigate the long-time progression-free surviving patient population treated with the ixazomib-lenalidomide-dexamethasone triplet. We retrospectively studied a total of 80 patients from 7 centers who received the triplet combination. Survival analyses were performed. Two-third of the patients responded: the overall response rate was 63.75%. 14 patients (17.5%) did not respond/had stable disease and 15 patients (18.75%) outright progressed upon therapy. Although progression-free survival was only 10.6 months for the entire patient cohort, the disease in a subgroup of 16 patients did not progress within two years. In fact, 11 of them were still in sustained remission after 3 years of therapy. Our goal was to analyze the characteristics of this subgroup. The idea of long-term therapy of multiple myeloma is gaining widespread acceptance. Therefore it is important to know which patients may benefit the most from certain therapies. Among these 16 long-term responder patients, reciprocal translocation of the immunoglobulin heavy chain seemed to lack an adverse impact on progression-free survival; comparable to trisomies, both curves had a progression-free plateau. The International Staging System (ISS) score at the start of therapy did not predict long-term survivorship. Most of the side effects in this subgroup were mild, manageable, none led to therapy discontinuation. Ixazomib-lenalidomide-dexamethasone was confirmed to be an effective and safe combination for relapsed, refractory multiple myeloma, and one-sixth of the treated patients were able to receive it for several years, effectively. This fully oral therapeutic option is at its best during the present COVID-19 pandemic. Orv Hetil. 2021; 162(36): 1451-1458.