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Methods: RRMM pts with ≥1 prior line of therapy (LOT) initiating a TpR on/after 1/1/2014 were followed retrospectively in Optum's de-identified electronic health record dataset ( 2007-2018) -a large US database. TpRs were categorized into B-,C-,D-,I-based; treatment groups were mutually exclusive. Median duration of therapy (DOT) and time-to-next-treatment (TTNT) were estimated using Kaplan-Meier methods and compared using stratified (by LOT) ± confounder adjusted Cox proportional hazard models. We used a repeated measures analysis of pt-LOTs with robust sandwich estimators to account for inclusion of pts in multiple LOTs. Observations were censored at time of loss to follow up (f/u)/end of study period (3/31/2018). A separate subgroup analysis of LOTs 2-3 was also performed. Results: Overall, 1345 pts with 1753 pt-LOTs (B-based, n = 746; C-based, n = 522; D-based, n = 269; I-based, n = 216) were included. B-/C-/D-/I-based TpRs consisted of an alkylator in 38/27/6/6% or an IMID-backbone in 58/71/93/94% (lenalidomide, 47/42/37/71%; pomalidomide, 7/28/55/21%; thalidomide, 4/1/1/2%), respectively; 81/60/37/63% pts received B-/C-/D-/I-based TpRs in LOT 2-3. Median age was 70/65/68/69 years and 33/20/25/38% pts were ≥75 years old in the B-/C-/D-/I-based TpR group, respectively. CRAB symptoms were more common in the B-/C-/D-(82/87/84%) than in the I-based group (64%) at baseline. Overall, more pts in the C-(26%) had high risk disease (del 17p and/or t(4;14) and/or t(14;16) and/or 1q21 gain), followed by D-(23%) vs in B-(16%) and I-based groups (14%), although 62/64/69/75% pts in each group had missing cytogenetic risk data. More pts in the D-based group (87%) were IMID and/or PI refractory, followed by C-(84%), I-(65%), and B-based (38%) groups. Double refractory status was present in 7/31/23/23% pts in the B-/ C-/D-/I-based groups. Overall, at median f/u of 16.3/13.3/8.6/10.2 months (mos) in the B-/C-/D-/I-based groups, unadjusted median DOTs were: 8.

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BACKGROUND: Real-world data can provide important information on the safety profile for recommended treatment options, but these data are collected infrequently. The ongoing post-authorization safety study (PASS) MM-034 (NCT03106324) is a prospective non-interventional study in patients (pts) with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible. This study allows for the collection of robust safety data for currently recommended regimens for the management of these pts. Global guidelines recommend lenalidomide (LEN) regimens, such as LEN plus dexamethasone (DEX; Rd) and LEN plus bortezomib (BORT) plus DEX (Vd), and BORT regimens, including BORT plus melphalan plus prednisone (VMP). METHODS: Transplant-ineligible adult pts with NDMM initiating therapy in centers throughout Europe are being enrolled in the ongoing MM-034 trial. Pts receiving any first-line regimen are eligible, but the decision for which treatment regimen will be used must be made prior to study inclusion. The primary endpoint is the incidence of cardiovascular events. Secondary endpoints include the incidence of renal impairment, infections, and second primary malignancies. In this analysis, the safety profiles of Rd, Vd, and VMP were compared. RESULTS: As of April 12, 2019, 145 Rd, 53 Vd, and 83 VMP pts were enrolled in the study (evaluable cohort). At the time of data cutoff, treatment was ongoing in 64.8% of Rd pts, 41.5% of Vd pts, and 61.4% of VMP pts. Median age was 79 years in Rd pts and 75 years in both Vd and VMP pts. The proportion of pts with ISS stage III disease was higher in the Vd group (24.8% Rd vs 32.1% Vd vs 24.1% VMP), and more pts in the VMP group were male (49.7% Rd vs 58.5% Vd vs 65.1% VMP). Adverse events (AEs) of all grades confirmed the expected side effects. Any-grade neutropenia occurred in 7.6%, 11.3%, and 13.3% of Rd, Vd, and VMP pts, respectively, and thrombocytopenia occurred in 6.2%, 5.7%, and 12.0%, respectively. However, any-grade febrile neutropenia was seen only in the VMP group, at 2.4%, but not in the other 2 groups. Any-grade polyneuropathy was reported in 1.4% of Rd pts, but in 18.9% of Vd pts and 19.3% of VMP pts. Any-grade infections of all kinds occurred in 28.3% of Rd pts, 41.5% of Vd pts, and 20.5% of VMP pts, with pneumonia in 3.4%, 11.3%, and 2.4% of Rd, Vd, and VMP pts, respectively. Any-grade thrombosis was reported in 4.8% of Rd pts and 3.8% of Vd pts and in no VMP pts. Grade 3/4 AEs occurred in 42.8% of Rd pts, 52.8% of Vd pts, and 43.4% of VMP pts. Grade 3/4 neutropenia was reported in 4.8%, 9.4%, and 8.4% of Rd, Vd, and VMP pts, respectively, and thrombocytopenia in 2.8%, 0%, and 8.4%, respectively. Grade 3/4 infections were lower in Rd pts (6.9% vs 24.5% Vd and 12.0% VMP); pneumonia, the most important of these, was reported in 0.7%, 5.7%, and 2.4% of Rd, Vd, and VMP pts, respectively. Grade 3/4 peripheral neuropathy was not seen in the Rd group; however, it was reported in 3.8% of Vd pts and 2.4% of VMP pts. Grade 3/4 venous thrombosis was reported in only 0.7% of Rd pts, with no events reported in the Vd and VMP groups. CONCLUSIONS: The results from this analysis, along with those from a previous analysis of cardiovascular events in the LEN-treated and non-LEN treated cohorts of pts from the European PASS MM-034 study (De Stefano, EHA 2019), provide real-world evidence for the safety profile of Rd as first-line therapy and support the role of Rd in the treatment of pts with NDMM who are transplant ineligible. Disclosures Cavo: celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tromp:Janssen: Other: Grant. Dhanasiri:Celgene Corporation: Employment, Equity Ownership. Kueenburg:Celgene: Consultancy. Rosettani:Celgene International: Employment. Martin:Celgene: Employment. Pozzi:Celgene: Consultancy. Bacon:Celgene: Employment, Equity Ownership. Gamberi:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Front-line treatment (of any type) was at the discretion of the investigator.

Patient: Male, 81-year-old Final Diagnosis: Chronic lymphocytic leukemia Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Hematology Objective: Unusual clinical course Background: Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm and the most common leukemia in adults in Western countries. Novel agents, including BTK inhibitors and the BCL2 inhibitor venetoclax, have dramatically changed the treatment landscape. Moreover, a disease flare, characterized by sudden worsening of clinical symptoms, radiographic findings of rapidly worsening splenomegaly or lymphadenopathy, and laboratory changes (increased absolute lymphocyte count or lactate dehydrogenase), is a phenomenon described in up to 25% of patients with CLL after ibrutinib discontinuation. We describe a patient with CLL with disease flare after ibrutinib discontinuation due to disease progression and describe the subsequent management of venetoclax initial treatment in the course of the disease flare. Case Report: We describe the case of an 81-year-old man with a 6-year history of CLL who was treated with multiple lines of therapy and developed worsening of disease-related signs and symptoms with fever, marked increase of lymphocyte count, acute worsening of renal function, and increase in lymph nodes and spleen size following cessation of targeted therapy with ibrutinib at the time of disease progression. There was subsequent overlapping of ibrutinib during the venetoclax dose escalation period to prevent disease flare recurrence. Conclusions: Our report highlights the problem of disease flare after ibrutinib discontinuation in order to avoid associated patient morbidity, underscoring the importance of awareness of this phenomenon and focusing on the addition of venetoclax at time of progression in ibrutinib-treated patients, as a temporary overlap strategy, to prevent disease flare.

MEITL is a very rare and highly aggressive peripheral T-cell lymphoma with poor prognosis and for which there is no standard treatment. Patients with relapsed/refractory disease have few treatment options and many still die of disease progression. Here we report the case of a 65-year-old woman affected by MEITL, progressing after initial treatment with an anthracycline-based chemotherapy and surgery, who received single-agent PEG-asparaginase salvage therapy at our institution. The treatment proved to be rapidly effective in controlling the disease and its associated paraneoplastic features. Nevertheless, toxicity was high and the patient died due to a treatment-related complication. The case we described brings new evidences on the effectiveness of PEG-asparaginase therapy in MEITL patients. Whether PEGasparaginase should be included in the treatment course of MEITL patients could be the subject of future studies.