Background Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of the polyomavirus John Cunningham (JCV) in the setting of immunosuppression. It has been described in patients with hematologic malignancies including multiple myeloma (MM), solid organ malignancies, granulomatous and inflammatory diseases, transplant recipients, lymphopenic patients (including patients with HIV) and with the use of certain drugs (rituximab, natalizumab). We present the first report to our knowledge of a patient with MM developing PML in association with daratumumab and pomalidomide therapy. Case Report A 63yo woman with relapsed/refractory IgA-Lambda MM on daratumumab and pomalidomide, presented to the emergency department after noticing difficulty putting her hair up in a ponytail. Her MM was diagnosed in 2003 and treated with steroids, high-dose melphalan and autologous stem cell transplant, maintenance therapy with thalidomide, switched to lenalidomide; upon relapse in 2010, she was treated with bortezomib, doxorubicin and dexamethasone, followed by bortezomib maintenance. Ten months prior to presentation, she relapsed and was started on daratumumab and pomalidomide, achieving an unconfirmed complete response (uCR), complicated by acquired hypogammaglobulinemia for the prior 8 months without infections. She developed progressive left arm weakness and gait instability; she denied any fevers, dysarthria, vision changes, headaches or seizures. On exam, she was alert and oriented; no cranial nerve abnormality; calculation, concentration and recall were intact; 4/5 strength in left upper extremity and 5/5 strength in all other extremities with preserved sensation and reflexes; coordination intact but a hemiparetic gait; rest of the exam was unremarkable. A brain MRI showed patchy and confluent areas of T2 hyperintense signal in the right greater than left cerebral hemispheres. She underwent a lumbar puncture which was positive for JCV by PCR (98 copies/mL) in her CSF and negative for neoplastic involvement by flow cytometry. The rest of her work-up was unremarkable. A diagnosis of PML was made and daratumumab and pomalidomide were discontinued. On follow-up brain MRIs four and eight weeks later, she had persistent extensive asymmetric patchy T2 hyperintense signal. Repeat LP revealed stable JCV in the CSF (95 copies/mL). Despite the lack of radiologic improvement, she had a remarkable clinical response with near resolution of neurologic symptoms and remains in an uCR. Discussion PML has been reported in association with multiple drugs used in the management of MM including corticosteroids, alkylating agents (cyclophosphamide, melphalan), immunomodulatory drugs (thalidomide, lenalidomide) and proteasome inhibitors (bortezomib, ixazomib), however, an association with pomalidomide or daratumumab has not yet been reported. In a clinical trial of daratumumab and pomalidomide for MM, a case of PML was reported, however, it was not considered to be related to these agents given that the patient received only one dose of daratumumab (Chari A. Blood 2017). PML has been reported in patients with primary hypogammaglobulinemia, however, it is not known whether acquired hypogammaglobulinemia - either due to MM or its therapy - is a risk factor for PML. Furthermore, the role for IVIG in the primary prevention or treatment of PML has not been clearly defined and warrants further study. The current treatment approach of PML remains the restoration of the host's adaptive immune response, including the discontinuation of immunosuppressive agents, unfortunately, evidence is lacking for any specific pharmacologic treatment. Recently, immune checkpoint inhibitors have shown clinical improvement or stabilization in small cohorts of patients with PML (NEJM 2019;380), however, given the safety concerns regarding their use in MM (KEYNOTE-183,-185) and the rapid clinical response seen in this case, no further therapy was instituted. This is the first report of pomalidomide and daratumumab as potential drugs associated with PML. Although it is not possible to ascertain their direct role in the reactivation of JCV, it should help clinicians recognize this potentially fatal complication in patients receiving either immunomodulatory drugs or anti-CD38 monoclonal antibodies, since prompt discontinuation may be life-saving. Disclosures Perry: Celgene: Speakers Bureau. Coleman:Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.

Background: Renal impairment is a frequent complication of multiple myeloma (MM) associated with poor prognosis and decreased overall survival; and can complicate drug dosing, limit treatment options and lead to a higher incidence of adverse events. Daratumumab is an anti-CD38 monoclonal antibody indicated for the treatment of patients with MM which does not require dose modification in the setting of renal impairment. Real-world data regarding its efficacy in patients with renal impairment and the rate of renal response are lacking. Methods: We performed a retrospective, single-center analysis of patients with relapsed/refractory MM treated with daratumumab as monotherapy or in combination with novel agents. Patients were grouped by renal function as calculated by their eGFR using the MDRD equation: <30, 30-59, >=60 mL/min/1.73m2. Renal response was defined as an eGFR >= 60 in two consecutive visits for patients with baseline renal impairment. Results: We identified 91 patients who started treatment with daratumumab between 2015-06-11 and 2018-08-16. The median age was 69 years old (range 40-93) and 25% were over the age of 75; 49 patients (54%) were female. Six patients (9%) were Hispanic, 16 (20%) were African American and 57 (71%) were Caucasian. High-risk cytogenetics were present in 58% of patients; defined as the presence of a complex karyotype, 1q gain, t(4;14), t(14;16), t(14;20) or del17p. Patients underwent a median of 5 prior lines of therapy (range 1-13), 45% had received an autologous stem cell transplant, 91% had been exposed to an immunomodulatory agent, 96% to a proteasome inhibitor, and 89% to both. Upon initial treatment, 53 patients (58%) had an eGFR >=60 mL/min/1.73m2, while 27 (30%) and 11 (12%) patients had an eGFR of 30-59 and <30 mL/min/1.73m2, respectively. The overall response rate (ORR) was 81% with a very good partial response (VGPR) or better of 47% and an unconfirmed complete response rate (uCR) of 23%. The median progression-free survival (mPFS) was 17.5 months while median overall survival (mOS) was not reached. There was no difference in mPFS or mOS between renal function groups. Of the 38 patients with baseline renal impairment (eGFR <60 mL/min/1.73m2), 11 patients (29%) achieved a renal response, however, none of these patients had severe renal impairment. When compared to patients with chronic renal impairment, those with acute renal impairment were more likely to achieve a renal response (80% vs 21%, p=0.02). No significant difference in mPFS or mOS was observed by renal response (mPFS: 25.7m vs 17.5m, p=0.2; mOS: NR vs NR, p=0.8). Each renal function group was well balanced for the above parameters, including adverse events of interest and concurrent myeloma therapy as shown in the table, except where indicated (*). Discussion: The results of this analysis provide comparable efficacy - independent of the degree of baseline renal impairment - to the results seen in clinical trials of combination therapy with daratumumab. Furthermore, the high renal response rate (29%) seen, as compared to the one in the subgroup analysis of ENDEAVOR (15%), highlights the utility of daratumumab in reversing renal end-organ damage in patients with relapsed/refractory MM without an increase in adverse events compared to patients with preserved renal function. These results suggest that daratumumab may be able to abrogate the adverse prognostic factor that impaired baseline renal function portends. A limitation of this study is its retrospective nature, the confounding effect of concurrent myeloma therapy and the small number of patients included with renal impairment. Table Disclosures Coleman: Merck: Research Funding; Pharmacyclics: Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding.

Background Renal impairment (RI) is a common complication and a negative prognostic factor in patients with Multiple Myeloma (MM). Patients with severe renal dysfunction may not benefit from optimal therapy as they are often excluded from autologous stem cell transplantation (ASCT). The aim of this study was to analyze the outcome of MM patients with prior RI undergoing ASCT and to evaluate the effect of transplant on renal and hematologic response. Methods From 147 eligible MM patients who underwent ASCT between 2002 and 2019, 131 were included in this single-center retrospective cohort study. Renal function (eGFR in ml/min/1.73m2 by MDRD) was evaluated at the time of MM diagnosis and prior to ASCT, as well as 30 and 100 days after ASCT. Patients were classified by renal function: A) eGFR <30; B) eGFR 30-59; or C) eGFR >60 prior to ASCT. ANOVA was used for comparison of renal function at diagnosis, at transplant, 30 days post ASCT, and 100 days post ASCT. Log rank testing was used for overall survival (OS) analysis of group A, B and C Results: Patients with renal dysfunction at baseline had lower ORR than controls to induction therapy, 71 v 78%. ASCT provided deepening responses to both groups, ORR 83 v 86% respectively. No renal responses were seen with ASCT, whereas 16% of patients with renal dysfunction at diagnosis had renal response prior to transplant. Of note, only 51% of patients with renal dysfunction received conditioning with Mel200, compared with 94% of control group. Overall survival benefit is seen for patients with eGFR>60 over any level of dysfunction (p = 0.0079). Conclusion Myeloma patients with renal dysfunction are a high risk group, and require special attention. Rapid and effective induction therapy remains an important step in reversing renal damage. In patients who do not recover kidney function, autologous stem cell transplantation should be considered, providing depth of response benefit. The conditioning regimen used for these patients warrants further investigation. Figure Disclosures Niesvizky: Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding. Coleman:Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau; Merck: Research Funding; Pharmacyclics: Speakers Bureau; Kite Pharmaceuticals: Equity Ownership. Rossi:BMS: Research Funding; Janssen, Celgene, Amgen: Consultancy.

Background: Autologous stem cell transplantation (ASCT) performed early in the disease course or at first relapse leads to improved progression-free and overall survival in transplant-eligible patients with multiple myeloma (MM). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF), when used after ASCT has been shown to accelerate time to neutrophil engraftment (TNE), and in some studies, it has been associated with reduced length of hospitalization, infectious complications, and antibiotic use. Strategies that reserve G-CSF administration to when neutrophil recovery is delayed, have attempted to show that there is no difference in infectious complications, length of hospitalization or TNE when compared to early administration of G-CSF on the day after stem cell infusion (DOT). However, the optimal timing for administering G-CSF has not yet been determined in patients with MM undergoing ASCT. Methods: This is a retrospective, single-center analysis of patients with MM undergoing ASCT from mobilized peripheral blood stem cells. Patients enrolled in a clinical trial of high-dose lenalidomide and melphalan as conditioning therapy which mandated the administration of filgrastim from day +1 after DOT (Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma, NCT01054196) were assigned to the early strategy group (ES). Patients receiving filgrastim as per our institutional guideline (starting on day +12 if ANC < 1000 cells/uL, or at the physician's discretion) were included in the delayed strategy group (DS). Patients were excluded from the analysis if their conditioning regimen included a different agent other than melphalan or lenalidomide. DOT was defined as the day of stem cell infusion. Date of neutrophil engraftment was defined as the first of three consecutive days with an ANC ≥ 500 cells/uL. TNE was calculated as the time from DOT to the date neutrophil engraftment. Total duration of neutropenia was defined as the time from onset of neutropenia (ANC < 500 cells/uL) to date of neutrophil engraftment. Length of hospitalization was defined as the time from DOT to the day of discharge. Results: We identified 59 patients in the ES group and 39 patients in the DS group from 08-16-2010 to 05-22-2019, for a total of 98 included in this analysis. Median age was 60 and 65 years in the ES and DS groups, respectively. Patients received a comparable dose of CD34+ cells, 5.05x106/kg in the ES group vs 4.66x106/kg in the DS group (p = 0.48). The ES group started filgrastim administration earlier (day +1 vs +9, p < 0.001) and received a greater median number of doses (10 vs 4, p < 0.001) as compared to patients in the DS group. Median time to neutrophil engraftment was shorter in the ES group compared to the DS group (10 vs 12 days, p < 0.001), as was the total duration of neutropenia (5 vs 6 days, p < 0.001). Documented infections were just as likely in both groups, 37% in the ES group and 39% in the DS group (p = 1). Length of hospitalization was shorter in the ES group as compared to the DS group (15 vs 17 days, p = 0.01). Discussion: Filgrastim use guided by an ES decreased the time to neutrophil engraftment, the duration of neutropenia and the length of hospitalization compared to a DS. Further analyses to identify predictive factors associated with a reduction in infectious complications and length of stay are underway, with the aim of developing a risk-adapted strategy for the use of filgrastim in patients with MM undergoing ASCT. Disclosures Van Besien: Miltenyi Biotec: Research Funding. Coleman:Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Rosenbaum:Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.