E. Bossi, F.A. Brioschi, C. Steidl, S. Baretta, S. Cantù, L. Verga, D. Fontana, G.G. Sharma, L. Mologni, L. Mussolin, R.G. Piazza, C. Gambacorti-Passerini
Facoltà di Medicina e Chirurgia Università degli Studi di Milano Bicocca, Clin- ica Ematologica Ospedale San Gerardo Monza, Dipartimento di Salute della Donna e del Bambino Università degli Studi di Padova, Istituto di Ricerca Pedi- atrica Città della Speranza Università degli Studi di Padova, Clinica di On- coematologia Pediatrica Università degli Studi di Padova, Italy
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK) and c- ros oncogene 1 (ROS1), is approved for treatment of patients with ALK- positive or ROS1-positive advanced non-small-cell lung cancer. However, ALK rearrangements, are also implicated in anaplastic large- cell lymphoma, mainly the fusion-protein NPM-ALK. ALK-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, develop in more than 50% of patients. In this ongoing, sin- gle-center, single-arm, phase II study, Crizotinib was administered as monotherapy with a starting dose of 250 mg twice daily to 11 ALK+ lymphoma patients who had progression of disease after at least one line of cytotoxic therapy. Patients were enrolled at the Department of Haematology, San Gerardo Hospital, Monza (Italy) from April 2015 to October 2018. Median number of previous cytotoxic treatments was 3 (range 2-6). Median age at diagnosis was 32 years (range 18-58 years) and 5/11 patients were male. The overall response rate (ORR) was 7 of 11 (63.6%; 95% CI = 35% to 85%). All responding patients achieved complete remission and negativity for the NPM-ALK transcript by Real Time Polymerase Chain Reaction (RT-PCR). Median follow up is 10 months (range 2-48). Disease status at the latest follow up is as follows: 6 patients are in complete response under continuous crizotinib admin- istration, 4 patients had progression of disease and died, 1 patient stopped the treatment and was in complete response after allogenic bone marrow transplantation. All relapses developed within the first 3 months of therapy.
Figure 1.
The two-years Progression Free Survival (PFS) and Overall Survival (OS, see attached Figure 1) are 65% (95% CI = 53% to 77%) and 70% (CI = 61% to 79%), respectively. The most common treatment related
adverse events were diarrhea (90.9%), oedema lower legs (100%), vom- iting (72.7%) and visual disorders (36.4%). All adverse events were Grade 1 or 2 and most of them were transient in nature. Crizotinib shows a good safety profile and carries out a potent antitumor activity with durable responses in advanced pretreated ALK+ lymphoma pa- tients. Crizotinib should be made available for patients with relapsed/refractory ALK+ lymphoma.
P020
FAVOURABLE OUTCOME OF PRIMARY MEDIASTINAL B-CELL LYMPHOMA (PMBCL) PATIENTS TREATED WITH R-DAEPOCH IN COMPARISON WITH AN HISTORICAL COHORT
A. Guidetti, L. Devizzi, V. Marasco, L. Farina, G. Perrone, A. Dodero, P. Corradini
Divisone di Ematologia Fondazione IRCCS Istituto Nazionale dei Tumori, Di- partimento di Oncologia ed Emato-Oncologia Università degli Studi di Milano, Italy
Background: In PMBCL patients (pts) R-DAEPOCH conferred long
lasting remissions without radiotherapy (RT) on mediastinum. In mostly young pts affected by PMBCL sparing the acute and late effects of RT is an important endpoint. We report clinical results of a consec- utive cohort of PMBCL pts treated with R-DAEPOCH and a compari- son with an historical PMBCL group.
Methods: Between 2010 and 2018, 41 PMBCL pts have been consec-
utively treated with 6 cycles of R-DAEPOCH at our Institution. Pts per- formed a baseline and end of treatment (EOT) CT and PET scan. R-DAEPOCH cohort has been compared with 32 pts treated before 2010 with Rituximab and anthracycline-based CT followed by RT (100%).
Results: Median age of 41 pts was 33 years (range, 18-63), 54% have
high LDH levels and 71% bulky disease. Only one patient interrupted treatment for progressive disease, 7 pts (17%) only received RT at EOT. With the exception of an higher proportion of stage III/IV patients in the historical group (42% vs 17%), all other clinical characteristics were similar between the two cohorts. With R-DAEPOCH febrile neutrope- nia was observed in 12% of pts, G3/G4 mucositis in 17% and acral neu- ropathy in 24%, no late cardiac toxicity was observed. Three pts of the historical cohort developed a second neoplasm outside the RT field (after 1 month, 4 and 12 years respectively). Median follow-up was 36 (range, 5-112) and 116 months (range, 7 - 188) for R-DAEPOCH and the historical cohort, respectively. Among R-DAEPOCH pts 3-years PFS and OS were 84% and 91%. EOT PET was negative [Deauville score (DS)1-3)] in 31 pts (76%) and positive (DS4) in 10 pts (24%). Pts with DS 4 at EOT PET had a poorer 3-years PFS, 44% vs 96% (p<0.0001) and OS, 63% vs 100% (p=0.0009) when compared to DS1-3 pts. Among DS4 pts, 4 received RT, 5 a salvage therapy, one no therapy after a second PET assessment revealing a decreased SUV value and 3 pts died for PD. In comparison to the historical cohort, R-DAEPOCH pts had a better 3-years PFS (84% vs 57%, p=0.02) whereas 3-years OS was not significantly different (91% vs 77%).
Conclusions: PMBCL pts treated with R-DAEPOCH have an excellent
prognosis without RT when achieve PET negativity at EOT, whereas pts with DS4 seems to be at high risk of progression and should be strictly monitored and considered for RT or salvage therapy. The PFS advantage observed in R-DAEPOCH could be affected by differences in disease stage between groups and should be confirmed in a larger cohort of pts.
Myeloma and Monoclonal Gammopathies 1
P021
TARGETING TLR4 OVERCOMES BORTEZOMIB RESISTANCE IN MYELOMA CELLS
C. Giallongo, D. Tibullo, G. Camiolo, A. Barbato, F. Puglisi, D. Cambria, N. Parrinello, A. Romano, C. Conticello, G. Li Volti, G.A. Palumbo, F. Di Raimondo
Divisione di Ematologia, AOU Policlinico Vittorio Emanuele, Biometec, Dipar- timento di Scienze Biomediche e Biotecnologiche, Università degli studi di Cata- nia, Dipartimento di Chirurgia generale e specialità medico-chirurgiche-Hematology section, Dipartimento di Scienze Mediche, Chirurgiche e Teconologie Avanzate “G.F. Ingrassia”, Università degli studi di Catania, Italy
Background: Multiple myeloma (MM) is a B-cell malignancy critically
dependent for survival and proliferation on signals coming from its in- flammatory microenvironment and toll-like receptors (TLR) may greatly contribute to inflammation. TLR are expressed on human MM cells and in particular TLR4 ligand promotes their proliferation and im- mune escape mechanisms. Since it has been demonstrated that the ac- quisition of proteasome inhibitors resistance involved increased mitochondrial respiration, we investigated the possible implication of TLR4 signaling with mitocondrial fitness as potential mechanism of drug resistance.
Results: The activation of TLR4 by LPS induced mitochondrial bio-
genesis by increasing PGC1, PRC and TFAM expression (p<0.01) and mitochondrial mass in MM cell lines (U266, MM1S, OPM2, H929). TLR4 expression was increased after Bortezomib (BTZ) treatment (p<0.001) and its signaling was functional as suggested by MyD88 up- regulation and MAPK activation. TLR4 protein was over-expressed in BTZ-resistant U266 (U266-R) cells compared to U266-S. Proteasome activity assay revealed that BTZ was still able to inhibit proteasome in U266-R in the same way as U266-S. Since U266-R showed higher mi- tochondrial mass and up-regulated TFAM, we investigated whether TLR4 was involved in resistance to BTZ going through mitochondrial fitness. U266-R cells were treated with either 15nM BTZ, 20 M TAK- 242 or their combination. Combinatorial treatment overcame resistance inducing 55% of apoptosis. Compared to BTZ alone, TAK-242/BTZ treated cells showed higher and extended ROS levels, less mitochon- drial mass and more depolarized mitochondria (p<0.001). Moreover, BTZ alone induced over-expression of NDUFA6 and ND4 (subunits of mitochondrial respiratory complex I), OPA1 and MNF2 (important in fusion process); on the contrary their expression decreased after com- bination with TAK-242 (p<0.001). Since increased ROS and mitochon- drial depolarization activate mitophagy, we evaluated co-localization of the autophagosome marker LC3 with mitochondria (stained with mitotracker) using confocal microscopy. TAK-242/BTZ increased mi- totracker/LC3 co-localization (p<0.01) and down-regulated SQSTM1 sensitizing resistant cells to apoptosis through the disruption of mito- chondrial aggregation and autophagic clearance of mitochondria.
Conclusions: Our data demonstrated that TLR4 inhibition in BTZ-re-
sistant cells impaired mitochondrial fitness resulting in apoptosis and overcoming of drug resistance.
P022
BORTEZOMIB-THALIDOMIDE-DEXAMETHASONE AND DOUBLE AUTOLOGOUS STEM CELL TRANSPLANTATION FOR NEWLY DIAGNOSED MULTIPLE MIELOMA: FINAL RESULTS OF THE PHASE 3 GIMEMA-MMY-3006 TRIAL
P. Tacchetti, E. Zamagni, F. Patriarca, M.T. Petrucci, L. Dozza, M. Galli, C. Crippa, F. Di Raimondo, L. Pantani, M. Offidani, S. Bringhen, F. Narni, V. Montefusco, R. Zambello, A. Spadano, C. Terragna, N. Pescosta, L. Baldini, G. Marzocchi, C. Cellini, D. Derudas, T. Caravita, M. Boccadoro, M. Cavo
Istituto di Ematologia Seragnoli Azienda Ospedaliero Universitaria S Orsola Malpighi Università di Bologna, Istituto di Ematologia Seragnoli Azienda Os- pedaliero Universitaria S Orsola Malpighi Univeristà di Bologna, Unità di Ema- tologia e Trapianto di Midollo Azienda Ospedaliera Universitaria S Maria Università di Udine, Dipartimento di Biotecnologie Cellulari e Ematologia Uni-
versità La Sapienza, Istituto di Ematologia Seragnoli Azienda Ospedaliero Uni- versitaria S Orsola Malpighi Università di Bologna, Divisione di Ematologia Ospedali Riuniti di Bergamo, Unità Operativa di Ematologia Spedali Civili di Brescia, Divisione di Ematologia AOU Policlinico Vittorio Emanuele Università di Catania, Istituto di Ematologia Seragnoli Azienda Ospedaliero Universitaria S Orsola Malpighi Università di Bologna, Dipartimento di Ematologia Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Divisione di Ematologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza Università di Torino, Dipartimento di Oncologia ed Ematologia Azienda Ospedaliero Uni- versitaria Policlinico di Modena, Divisione di Ematologia Fondazione IRCCS Istituto Nazionale dei Tumori, Ematologia e Immunologia Clinica Azienda Os- pedaliera di Padova, UO Ematologia Clinica Ospedale Civile Spirito Santo, Is- tituto di Ematologia Seragnoli Azienda Ospedaliero Universitaria S Orsola Malpighi Università di Bologna, Divisione di Ematologia e Centro Trapianto Midollo Osseo Ospedale Regionale Generale, Fondazione IRCCS Cà Granda Unità di Ematologia Ospedale Maggiore Policlinico Università di Milano, Istituto di Ematologia Seragnoli Azienda Ospedaliero Universitaria S Orsola Malpighi Università di Bologna, Unità di Ematologia Ospedale S Maria delle Croci, Strut- tura Complessa di Ematologia e Centro Trapianti di Cellule Staminali Emopoi- etiche Ospedale Oncologico A Businco, Ematologia Ospedale S Eugenio, Divisione di Ematologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza Università di Torino, Istituto di Ematologia Seragnoli Azienda Os- pedaliero Universitaria S Orsola Malpighi Università di Bologna, Italy
This final analysis of the phase 3 GIMEMA-MMY-3006 trial compar- ing bortezomib-thalidomide-dexamethasone (VTD) versus thalido- mide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed multiple myeloma (MM), was performed to evaluate long-term outcomes at a median follow-up for surviving patients (pts) of 124.1 months. 474 pts were enrolled and randomly assigned to VTD (236) or TD (238) arms. 10-year progression free survival (PFS) and over- all survival (OS) rates for the VTD and TD subgroups were 34% versus 17% (median, 60 versus 41 months, HR=0.62, p<0.001) and 60% versus 46% (median not reached versus 110 months, HR=0.68, p=0.007), re- spectively, representing a 38-32% reduction in the risk of progression and death with VTD. Randomization to VTD was an independent fac- tor predicting for prolonged PFS (HR=0.60, p<0.001) and OS (HR=0.66, p=0.010). Among pts who received subsequent therapies, the 2nd PFS was similar following VTD or TD (median, 21 and 19 months). Con- versely, PFS2 was longer for pts on VTD than on TD, with median val- ues of 113 and 74 months (HR=0.64, p<0.001), respectively. Multivariable analysis not including therapy identified high risk cyto- genetic abnormalities [t(4;14) and/or del(17p)], ISS stage II/III, and fail- ure to achieve complete response (CR), as leading factors adversely affecting survival. Low-risk (LR) (22%), intermediate-risk (IR) (39%) and high-risk (HiR) (39%) groups were identified by the presence of none, a single or at least two adverse variables, respectively. These three categories showed divergent PFS and OS curves within each treatment arm (p<0.001). Based on conditional survival CS(t|s) estimate for PFS, the probability of surviving 2 years further without progression im- proved progressively after 36 months (p value for trend=0.009). The 2- year conditional PFS became similar after 78 months for LR and IR groups (87% and 86%, respectively), but proved significantly lower in HiR (63%) (p=0.008). The incidence of second primary malignancies per 100 person-years was 0.87 on VTD and 1.41 on TD. In conclusion, this final analysis of the GYMEMA MMY-3006 trial confirmed a per- sistent PFS benefit and revealed extended OS for pts in the VTD arm without new safety concerns. Cytogenetics, ISS stage and achievement of CR provided a prognostic model for survival. A PFS time of 78 months predicted for long-term survival outcomes in LR and IR groups.
P023
DARATUMUMAB IN HEAVILY PRETREATED, TRANSPLANT INELIGIBLE, AL AMYLOIDOSIS PATIENTS: A SINGLE CENTRE EXPERIENCE
M. Riva, G. Scapinello, L. Ammirati, F. Lessi, A. Branca, R. Zambello, F. Piazza, G. Semenzato, T. Berno
Department of Medicine, University of Padua, Hematology and Clinical Im- munology Unit, Italy
Introduction: Immunoglobulin light chain (AL) amyloidosis is a het-
come, especially in advanced organ involvement. Patients with re- lapsed/refractory disease after first line therapy represent an unmet clin- ical need. The high efficacy of immunotherapy could be a valuable rescue option.
Methods: We retrospectively analysed 10 AL amyloidosis patients,
transplant ineligible, with cardiac, renal and multiorgan involvement, treated with Daratumumab in our Unit. Hematological and organ re- sponses were assessed according to Amyloidosis Consensus Criteria. Patients characteristics are shown in Table 1. Six patients (60%) had cardiac and renal involvement. Among patients with cardiac involve- ment, patients with stage III and IV were 3 (30%) and 2 (20%); renal stage I and II were 6 (60%) and 4 (40%). 9 patients (90%) had lambda and 1 (10%) kappa light chain.
Table 1. Patients characteristics.
The FISH analysis demonstrated t(11;14) and gain1q21 in 1 (10%) and 3 (30%) patients, respectively; cytogenetic was normal in 6 (60%) patients. Immunoparesis was observed at diagnosis in all of them. All patients had multiple myeloma and amyloidosis: 8 (80%) patients Durie Salmon stage 1A, 2 (20%) DS3A. Median plasma cell bone mar- row infiltration was 35% at diagnosis. AL amyloidosis was proved by immunoelectron microscopy in 10 patients (8 abdominal fat pad biopsy, 1 endomyocardial biopsy and 1 skin biopsy). After bortezomib-based regimen and immunomodulatory therapy in all of them, we started Daratumumab in this setting. Best hematologic response was ≤VGPR to any prior therapy (1 VGPR, 5 PR and 4 no response by day 30; 1VGPR, 6 PR and 3 no response at the end of therapy). Daratumumab induced depth and rapid responses, resulted in 4 CR, 1 VGPR, 5 PR and organ response in 6 (60%) of them, with good tolerance, without rele-
vant adverse event (only one urosepsis). We observed only one death due to sudden cardiac arrest, in a patient who was in PR after Daratu- mumab.
Conclusions: In our experience, immunotherapy is safe and highly ef-
fective, also in patients with a more aggressive disease at diagnosis (ad- vanced cardiac and renal involvement, and immunoparesis). These data could suggest that this group of patients may probably require the use of immunotherapy early in the disease course to prevent an irreversible organ involvement due to the direct proteotoxicity of amyloidogenic light chains.
P024
IMMUNE PROFILING OF PLASMA CELL DYSCRASIAS REVEALS AN EXTREME T-CELL MODULATION IN TREATED MULTIPLE MYELOMA PATIENTS
G. Barilà, L. Pavan, S. Vedovato, T. Berno, A. Branca, A. Teramo, G. Calabretto, S. Manni, V. Trimarco, S. Carraro, M. Facco, F. Piazza, G. Semenzato, R. Zambello
Department of Medicine (DIMED), Hematology and Clinical Immunology sec- tion, Padua University School of Medicine, Padua, Italy
Multiple Myeloma (MM) is a hematological malignancy always pre- ceded by a not malignant precursor state defined monoclonal gam- mopathy of undetermined significance (MGUS) and by a asymptomatic MM (smouldering MM, sMM). Immune dysfunction plays a key role in the pathogenesis of the disease, as demonstrated by the prognostic role of immunoparesis in the progression of MGUS and sMM into ac- tive MM (aMM). The aim of this study is to analyze the immune sub- sets distribution into plasma cells dyscrasias. A total amount of 895 bone marrow samples (170 MGUS, 188 sMM, 586 aMM) of 714 pa- tients affected by plasma cells dyscrasias were studies at the different time point by flow cytometry for CD3, CD4, CD8, CD16, CD19, CD56, CD57, HLA-DR and GD antigens. By flow, CD3+ T cells, CD19+ B cells and CD3-/CD16+/CD56+ NK cells were initially studied in MGUS (n=170), sMM (n=188) and active MM (250 newly diagnosed and 286 treated) patients. In aMM cases, no significant differences were found in total T and NK cells percentages towards sMM (73.2±12.5 vs 72.4±10.3, p=0.6717 and 14.8±8.9 vs 14.1±7.9, p=0.5676) and MGUS cases (73.2±12.5 vs 71.9±9.0 p=0.3336 and 14.8±8.9 vs 13.3±7.3, p=0.1205) while B cells were lower, although significantly only towards MGUS (9.8±9.1 vs 10.7±5.9, p=0.2955 and 9.8±9.1 vs 12.3±7.1, p=0.001). A more detailed analysis of T cell subsets evidenced that aMM patients were characterized by lower percentages of CD4+ T cells (32.9±12.9 vs 39.9±9.5, p=0.0001 and 32.91±12.9 vs 38.4±8.6, p=0.0001) and higher percentages of CD8+ lymphocytes (45.1±14.1 vs 38.8±10.0, p=0.0001 and 45.1±14.1 vs 38.7±9.9, p=0.0001), CD8+/DR+ lympho- cytes (9.7±13.1 vs 4.1±4.7, p=0.0001 and 9.7±13.1 vs 3.8±4.5, p=0.0001) and CD3+/CD57+ lymphocytes (18.9±12.7 vs 14.5±9.2, p=0.0001 and 18.9±12.7 vs 13.6±8.8, p=0.0001) while no significant differences were found in CD3+/GD+ cells (3.6±4.0 vs 4.2±3.6, p=0.2872 and 3.6±4.0 vs 4.2±3.2, p=0.2638). Interestingly, all these differences were mostly at- tributed to treated patients towards newly diagnosed MM (CD4+ cells= 27.0±12.1 vs 39.5±10.3, p<0.0001, CD8+ cells=50.5±14.6 vs 39.0±10.5, p<0.0001, CD8+/DR+ lymphocytes=14.1±15.8 vs 4.5±4.7, p<0.0001 and CD3+/CD57+ lymphocytes=21.7±13.5 vs 15.8±10.9, p<0.0001). Our results demonstrated a profound T cell immune-modulation in ac- tive MM patients towards MGUS and sMM precursor states. Moreover, most of these changes are therapy-related, indicating that Myeloma treatment can shape the T cell compartment.
P025
SAFETY OF RAPID DARATUMUMAB INFUSION IN RELAPSED AND REFRACTORY MULTI- PLE MYELOMA
E. Attardi, E. Antonioli, M. Staderini, M. Messeri, A. Buzzichelli, V. Nencini, A. Fani, A. Bosi
Haematology Unit, AOU Careggi, Florence, Italy
Daratumumab is a human CD38 monoclonal antibody approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). Currently, it can be used as a monotherapy at second relapse and in combination with desametasone and bortezomib (Dara-VD) or lenalidomide (Dara-RD) at first relapse. Daratumumab displays an ex-
cellent safety profile. Mild-graded infusion-related reactions (IRRs) occur mostly during the first infusion. For this reason, recommended administration rates provide a timing of 6.5, 4.5 and 3.5 hours respec- tively for the first, second, and following infusions. In our practice, we observed a low rate of adverse reactions also in patients with advanced disease. This is a single-center study exploring the safety of a rapid dara- tumumab infusion. Inclusion criteria was having at least eight previous doses of daratumumab, administered per standard procedure. Previous IRR was not an exclusion criterion. We evaluated 20 consecutive pa- tients (median age 65 years, M:F rate 1:1, MM IgG 45%, IgG 10%, IgA 15%, IgA 10%, micromolecular 10%, micromolecular 5%) affected by RRMM. Six patients (30%) were treated with daratumumab single agent, 3 patients (15%) with Dara-VD and 11 (55%) with Dara-RD. Moreover, 25% of patients suffered from a cardiovascular disease (hy- pertension, arrhythmia or valvulopathy). All patients had received pre- medication with chlorphenamine, paracetamol and corticosteroid; during first infusion, 14 patients (70%) had suffered of IRRs, grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE). Common IRRs included conjunctivitis, rhinorrhoea, cough, wheezing or hypertension, reverted in a short time. Median number of daratumumab prior infusions for our cohort was 14. Premedication was carried out similarly to previous infusions. Short time infusion was re- alised administering daratumumab at rate of 200 ml/h for the first 30 minutes, increasing to 400 ml/h for the next 60 minutes. No patient ex- perienced adverse events during infusion, neither 30 min after comple- tion, in which patients were observed to assess for delayed IRRs. 90-min infusion were realised in safety even in patients who experi- enced grade I (40%) and II (10%) anaemia or in those with a history of immediate hypersensitivity reactions (20%) to drugs or aeroallergens. Ninety-minutes daratumumab infusion was therefore well tolerated, allowing a considerable saving of time for RRMM patients and encour- aging their adherence to treatment.
P026
A REAL-WORLD EFFICACY AND SAFETY ANALYSIS OF CARFILZOMIB-LENALIDOMIDE- DEXAMETHASONE (KRD) COMBINATION IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)
I. Caratozzolo, P. Tacchetti, R. Zambello, L. Pantani, E. Antonioli, K. Mancuso, G. Buda, S. Rocchi, L. Canepa, I. Rizzello, B. Gamberi, G. Barilà, N. Testoni, G. Marzocchi, E. Zamagni, M. Cavo
Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Azienda Ospedaliero- Universitaria S. Orsola-Malpighi, Azienda Ospedaliera di Padova e Veneto, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Azienda Ospedaliero Univesitaria Careggi, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Azienda Ospedaliero Universitaria Pisana, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Azienda Ospedaliera ASMN, Azienda Ospedaliero-Uni- versitaria S. Orsola-Malpighi, Azienda Ospedaliera ASMN, Azienda Os- pedaliera di Padova e Veneto, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Azienda Ospedaliero- Universitaria S. Orsola-Malpighi, Italy
Carfilzomib-lenalidomide-dexamethasone (KRd) has been approved for the treatment of relapsed/refractory multiple myeloma (RRMM), based on results of the ASPIRE trial (Stewart, N Eng J Med, 2015). In this retrospective analysis, we aimed at further evaluating the efficacy and safety of KRd in a real-world setting. 197 RRMM patients (pts) who received KRd in routine care between January 2016 and March 2018 in 6 italian haematologic institutions were identified and followed for a median of 12.5 months. At KRd initiation, median age was 63 years, 47% of the pts had ISS II or III, and 27% carried high risk cytogenetic abnormalities (HRCA) [del17p and/or t(4;14) and/or t(14;16)]. Median number of prior lines of therapy was 2 (1-8); nearly all pts (96%) re-