ALBERT

Description: Background: The incidence of MM is 2 to 3 fold higher in blacks than in whites; they present at a younger age and have better overall survival. The biological bases for these disparities remain unclear. Outcome of MM is linked to cytogenetic and molecular changes, both primary (hyperdiploidy and heavy chain (IgH) translocations) and secondary (rearrangements of MYC, activating mutations of NRAS, KRAS or BRAF, and deletions of 17p). Methods: Cytogenomic alterations in consecutive MM patients were assessed using integration of metaphase chromosome analysis by GTG-banding and interphase fluorescence in situ hybridization (iFISH) in CD138-positive cells isolated from fresh BM samples using a protocol of magnetic-activated cell sorting. Changes evaluated included monosomy 13/del(13q), monosomy 17/del(17p), gain of 1q21, and rearrangements of the IGH gene including t(4;14), t(11;14) and t(14;16). Results: Samples from 218 consecutive MM patients were analyzed (Table 1). 108 were from black and 110 were from white patients. Median age for blacks was 59 years (range: 36 - 82) and for whites, 63 years (range: 39 - 83) (p=0.008). Fewer black men than whites were observed (46.3% versus 64.6%, p=0.007). Overall, blacks had fewer abnormal karyotypes compared to whites (18.1% versus 31.8%; p=0.02). Black patients had a lower frequency of non-hyperdiploid karyotypes (8.5% versus 20.6%; p=0.01) and had a trend toward lower frequencies of rearrangements of IGH (30.8% versus 43.5%; p=0.055) than white patients. Most notably, they had significantly lower frequencies of monosomy 17/del(17p) (5.6% versus 18.5%; p=0.003) and monosomy 13/del(13q) (28.9% versus 46.3%; p=0.008). After stratification by age (Figure 1), younger patients showed significantly higher frequencies of the monosomy 17/del(17p) abnormality (p=0.001) and the t(4;14) (p=0.04) than older patients, with the difference more significant in white patients. The associations among molecular cytogenetic abnormalities (Figure 2) showed a different association pattern for black and white patients. White patients with t(11;14) were more likely to have monosomy 13/del(13q) (p=0.003) and gain of 1q21 (p=0.02), while this association was not observed in black patients. Conclusion: Black MM patients had significantly different cytogenetic profiles detected by iFISH on CD-138 selected malignant cells, compared to whites. Black MM patients had a more favorable profile, including lower frequencies of non-hyperdiploid karyotype and of IGH rearrangements. This study supports a biological basis for previously described outcome disparities between black and white patients with MM. Further studies will focus on identifying specific molecular targets and their impact on therapy and on overall outcome. Table 1. Demographics and cytogenetic abnormalities of the MM patients Demographics Black White P-value# Total, n 108 110 Gender, n (%) =0.007* Male 50 (46.30%) 71 (64.55%) Female 58 (53.70%) 39 (35.45%) Age (median) 59 63 =0.008* Chromosome (karyotype) =0.022* Normal 86 (81.90%) 73 (68.22%) Abnormal 19 (18.10%) 34 (31.78%) Hyperdiploidy 8 (7.6%) 8 (7.4%) Non-hyperdiploidy 9 (8.5%) 22 (20.6%) =0.013* 11;14 translocation 2 (1.9%) 4 (3.7%) FISH abnormality -13/del(13q) 31 (28.97%) 50 (46.30%) =0.008* Gain of 1q21 35 (32.71%) 47 (43.52%) =0.103 -17/del(17p) 6 (5.61%) 20 (18.52%) =0.003* IGH rearrangements 33 (30.84%) 47 (43.52%) =0.055^ t(4;14) 7 (6.54%) 13 (12.38%) =0.146 t(11;14) 15 (20.55%) 15 (19.48%) =0.870 t(14;16) 2 (3.85%) 6 (10.71%) =0.175 others 16 (14.95%) 15 (13.89%) =0.824 *means statistical significant (p-value 〈 0.05), where ^ means marginal significant (0.05 〈 p-value 〈 0.10). #p-values come from the Cochran-Mantel-Haenszel tests for categorical variables, and t tests for continuous variables. Associations among eight molecular cytogenetic abnormalities. Each solid black line indicates one abnormality is statistically significantly associated with another abnormality. Figure 1. Distributions of cytogenetic abnormalities by age and race Figure 1. Distributions of cytogenetic abnormalities by age and race Figure 2. Relationship of various cytogenetic abnormalities in the MM patients Figure 2. Relationship of various cytogenetic abnormalities in the MM patients Disclosures No relevant conflicts of interest to declare.

Description: Abstract 5110 Background: PBK/TOPK (PDZ-binding kinase, T-LAK-cell-originated protein kinase) is a serine-threonine kinase that was originally cloned as an IL-2 inducible gene exclusively expressed in cytotoxic T lymphocytes, and an interaction partner with the human tumor suppressor hdlg. PBK/TOPK mRNA has been found to be expressed in normal testicular and embryonic tissues, proliferating neural progenitor cells and various tumor cell lines. Numerous studies have demonstrated that PBK exerts its proproliferation function by phophorylating and thus activating its substrate proteins p38, ERK2, LGN/GPSM2, and histone H3, which are involved in cell growth, cell cycle progression and chromatin remodeling. Recently, we further reported that PBK could interact with tumor suppressor p53 via its DNA binding domain and impair its function as a transcription factor (Oncogene, 2010). These lines of evidence all point to PBK as a novel multifunctional oncoprotein. Study Aim: To investigate the frequency of PBK expression in hematological malignancies. Methods: Immunohistochemistry for PBK expression on various tissue microarrays (US Biomax) was performed. Briefly, paraffin-embedded tissue microarrays were treated with xylene and ethanol followed by a protein-blocking reagent. After incubation with 1:50 diluted PBK antibody (Cell Signaling) and HRP-labeled-secondary antibody (US Biomax), the tissue microarrays were stained with substrate DAB. The slides were scored according to the following criteria: 0 (negative), 75% cells were stained. Results: In 108 cases of diffuse large B-cell lymphoma, 50% were positive for PBK, among which 27 scored +1, 21 scored +2, and 6 scored +3; in 8 cases of Burkitt lymphoma, 7/8 (87.5%) were positive for PBK with all of them scoring +3; in 58 cases of Hodgkin lymphoma, 67% were positive for PBK with 35 scoring +1 and only 4 scoring +2; in 9 cases of plasma cell myeloma, only 2 were positive for PBK and both scored +1. Three follicular lymphomas and 4 reactive lymph nodes scored 0. Conclusions and Future Directions: PBK protein was highly expressed in a high proportion of Burkitt lymphoma. PBK was also expressed in a relatively high proportion of diffuse large B-cell lymphoma and Hodgkin lymphoma, suggesting that PBK is implicated in the pathogenesis of hematological malignancies with higher proliferation rates. PBK expression was much less frequent in more indolent hematologic neoplasms such as myeloma and follicular lymphoma. Our lab is now working on the crystal structure of PBK with the long-term goal to identify small molecular inhibitors of PBK function. These new results in combination with our earlier data suggest that inhibition of PBK function may be a rational strategy to sensitize aggressive/highly proliferative hematologic neoplasms to anti-neoplastic therapy. Disclosures: No relevant conflicts of interest to declare.

Description: Background: There are no prospective studies that define best therapy for DHL (presence of c-MYC and BCL-2 translocations) or DEL (co-expression of c-MYC ³40% and BCL-2 ³50% by IHC). Retrospective data for both entities show suboptimal outcomes with R-CHOP and perhaps improved outcomes with intensified regimens such as DA-EPOCH-R. We conducted a phase I prospective multicenter study adding escalating doses of LEN to DA-EPOCH-R in pts with DHL or DEL. Herein, we report the final results of the dose-finding portion of this ongoing clinical trial. Patients and Methods: Eligible pts had DHL or DEL as defined above. They were allowed to receive radiotherapy for neurologic compromise or one cycle of R-CHOP prior to enrollment at the investigator's discretion. Pts had measurable disease, ECOG PS 0-2, and adequate liver, kidney, and marrow function and no known HIV or CNS involvement. Either aspirin or warfarin prophylaxis was required. Primary objective was to determine the maximum-tolerated dose (MTD) of LEN when added to DA-EPOCH-R. We utilized a standard (3+3 design) where LEN was started at 10mg (days 1-14, Q21-days) with each cycle of DA-EPOCH-R, and escalated to a maximum of 25 mg unless a MTD was reached at an earlier dose. Dose-limiting toxicities (DLTs) were assessed during cycle 1; DA-EPOCH-R administration and dose modifications were conducted as per usual protocol. Cycles were repeated every 3-weeks for a maximum of 6 cycles and were followed by an end of therapy PET scan. CNS prophylaxis was strongly encouraged with 12.5 mg IT-methotrexate for 4 doses during induction. Patients attaining PET negativity after induction were continued on maintenance LEN 10 mg (days 1-14 Q21 days) for 12 cycles. During the LEN dose escalation portion of the study, a hematologic toxicity did not count as a DLT to allow DA-EPOCH-R dose adjustments. Results: 15 pts (6: DHL and 9: DEL; 13 DLBCL and 2 BCL-U) were enrolled; median age was 62 years (range: 26-83). There were 5 males and 10 females (11 whites, 3 African Americans, and 1 Asian pts). Two pts had ECOG PS 2 while all others were 0-1. All pts (100%) had stage III/IV disease, 13 pts (86%) had high-risk IPI score, and median LDH was 673 (range: 193-1,835). All ptsare assessable for toxicity. Serious adverse events (SAEs) per dose levels are summarized in the Table. DA-EPOCH-R dose escalation was feasible in 10 pts (67%), one pt (6.7%) maintained the same dose throughout, and another (6.7%) required dose de-escalation. Two DLTs were observed (grade 4 sepsis and hypotension for both) at dose-level 20 mg of LEN leading to 15 mg being the MTD and RP2D. Most common grade 1 and/or 2 non-hematologic toxicities were fatigue (70%), constipation (47%), alopecia (53%), nausea (47%), peripheral sensory neuropathy (40%), diarrhea (33%), and hypokalemia (33%). The only grade 3 and/or 4 non-hematologic toxicity occurring in ³2 pts (13%) was hypokalemia. All others occurred in 1 pt (6%) and were: constipation, fever, hyperglycemia, hypertension, mucositis, and hypoalbumenemia. One pt (6%) developed treatment-related myelodysplasia, (T-MDS), 18 months after treatment initiation. Twelve patients are evaluable for response at time of analysis, (1 patient lost to follow-up, and 2 with ongoing therapy). Best responses at completion of induction based on PET were 6 complete responses (CR: 50%), 3 partial responses (PR: 25%) and 1 pt with progressive disease (8%). All CR pts received LEN maintenance but only 1 completed 12 cycles to date (1 came off due to cytopenias found later to have T-MDS, 1 due to AE, 1 due to finding of unrelated colon cancer, 2 on active maintenance). With median follow up 10.7 months (range: 1.3-18.6 months), 14 pts remain alive and one pt has died for an OS of 93%. Conclusions: LEN can safely be added to DA-EPOCH-R in DHL and DEL patients at a dose of 15 mg (days 1-14 Q21 days). Chemotherapy dose escalation was not compromised and preliminary safety/efficacy data appear promising. A phase II study in this pt population with LEN+DA-EPOCH-R is underway. Disclosures Nabhan: Celgene, Genentech, Seattle Genetics, Astellas: Research Funding; Celgene, Genentech, Abbvie, Infinity, Cardinal Health: Consultancy. Karmali:Celgene: Speakers Bureau. Fishkin:Biogen: Other: Owns Stocks. Smith:Genentech: Consultancy, Other: on a DSMB for two trials ; Juno: Consultancy; TGTX: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; Amgen: Other: Educational lecture to sales force; Portola: Consultancy; Celgene: Consultancy; Pharmacyclics: Consultancy.

Description: Introduction Axi-cel is an autologous anti-CD19 CAR T-cell therapy approved by the US FDA 10/18/2017, for the treatment of adults with relapsed or refractory (r/r) large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed lymphoma (tFL), and high-grade B-cell lymphoma (HGBCL) who have failed at least two prior systemic lines of therapy. In the pivotal ZUMA-1 trial, 108 patients (pts) with r/r DLBCL were treated with axi-cel: the best overall response rate (ORR) was 82% and complete response (CR) rate was 58%. At a median follow-up of 15.4 months, 42% of the pts had ongoing remission (Neelapu and Locke et al. NEJM 2017). Grade 3 or higher cytokine release syndrome (CRS) by Lee criteria and neurologic events (NEs) occurred in 13% and 31% of the pts, respectively. Here, we evaluated the real world outcomes of pts treated with standard of care axi-cel under the commercial FDA label. Methods and Results Seventeen US academic centers contributed data to this effort independently of the manufacturer. As of 6/30/2018, 211 pts were leukapheresed with intention to manufacture commercial axi-cel. Of these, 165 (78%) pts completed axi-cel infusion as of 6/30/18 and a further 23 (11%) pts are scheduled for axi-cel infusion in July 2018. Of the 23 remaining pts, 7 (3%) received axi-cel therapy on ZUMA-9 expanded access trial (NCT03153462) due to non-conforming cell therapy product, 15 (7%) pts died before axi-cel infusion (14 from lymphoma progression and 1 from sepsis) and 1 (1%) patient attained CR from bridging therapy and was not infused. Safety was evaluable in 163 pts receiving axi-cel. Grade ³3 CRS and NEs occurred in 7% and 31% of pts. Tocilizumab was administered in 62% of pts and 57% received corticosteroids. Outside of lymphoma progression, 3 deaths occurred post-axi-cel; 1 due to HLH, 1 due to systemic candidiasis, and a third due to septic shock. There were no grade 5 NEs observed. Response assessment was done for pts infused with axi-cel and who were re-staged at day 30 and/or day 100, or were deemed to have clinical progression. Of 112 pts evaluable at day 30, ORR was 79% with 50% CR, 29% PR, 6% SD and 14% with PD. Of 39 pts evaluable at day 100, 59% of pts had ongoing response (CR 49%, PR 10%). At the time of abstract submission, more detailed patient characteristics and treatment course data were available in 134/165 pts infused. Median age was 59 (range 21-82) with 57% male. Performance status (PS) was ECOG 0-1 (81%), ECOG 2 (16%) and ECOG 3 (3%). By histology, 61% of pts had DLBCL including HGBCL, 31% had tFL and 8% PMBCL. Thirty-one percent had a prior autologous stem cell transplant. Bridging therapy between apheresis and infusion was given in 56% of patients, the majority of which consisted of chemotherapy. Sixty-six of 134 (49%) would not have met eligibility criteria for ZUMA-1 at the time of leukapheresis. Common criteria that would have made these patients ineligible for ZUMA-1 included ECOG PS 〉1 (n = 22), platelets

Description: Background African Americans (AAs) have a higher incidence of MM, about twice as much as Caucasians, and present at a younger age. Several studies have shown that presentation and outcomes of AA are similar to Caucasians treated with standard and high dose chemotherapy. The impact of induction with novel agents (IMIDs and proteosome inhibitors) and prognostic markers such as cytogenetics on different ethnic groups has not been fully evaluated. Methods We analyzed MM patients (AA=174 and Caucasians= 279) who underwent auto-SCT over fifteen years (1998-2013). Baseline characteristics are summarized in table below. Patients received induction therapy with standard chemotherapy (n=33) or dexamathesone (n=43) before 2001 or IMIDs or protesome inhibitors in addition to either chemotherapy (n=72) or dexamethasone (n=203) when treated after 2001. All patients received high-dose melphalan followed by auto-SCT. Response criteria were assessed according to the International Uniform Response criteria. Results AA were significantly younger but with no differences in disease stage or CRAB criteria at MM diagnosis with the exception of anemia. More AA women were referred and underwent auto-SCT relative to AA men. The subtype distribution was significantly different between AA and Caucasians (P

Description: Background: The role of metabolism in outcomes of cancer patients is under investigation. A higher body mass index (BMI) substantially increases the risk of cancer and impacts the treatment. High BMI is also associated with increased risk of MM (Euro J Cancer 2011). However no data is available in the effect of BMI on myeloma survival after autologous stem cell transplantation (ASCT) Methods: We retrospectively reviewed patient charts who had ASCT between Jan 2010 - November 2011. Patients were selected if they have adequate data, two lines of induction treatment prior to transplantation. Most of the patients received maintenance treatment. IRB granted exemption for anonymous data collection. We collected demographic data, cytogenetic risk, response with induction and after transplant, progression free and overall survival. BMI was estimated at the time of ASCT. Results: A total of 223 post ASCT myeloma patients met inclusion criteria. Median age of the cohort was 58 years, 48.8% were African-American, 51% Caucasian, 1% Asian, and 0.5% Hispanic. Median BMI was 29.7 and 30 in female and males respectively. Median BMI was 29.4 in Caucasians and 29.6 in African-American cohorts. 24% of patients had high risk cytogenetics. 72% of patients experienced very good partial response (VGPR) or better post-transplant. On multivariate analysis, PFS and OS showed no association at any of the four BMI levels (p=0.573), age, gender, race, or depth of response. High risk cytogenetics was associated with PFS (p= 0.022). There was no association with high risk cytogenetic features at any BMI level, age, gender, race (p=0.245). For patients with BMI 〉 40, PFS differed significantly when compared to patients with normal BMI: 37 months versus 50, p=0.52. Unadjusted hazard ratio (HR) 2.10 (95% CI: 0.62-7.18) with respect to patients with normal BMI. Subgroup multivariate analysis with patients with morbid obesity did not show any association with depth of response (partial response or VGPR or better) or high-risk cytogenetic features. Conclusion: BMI as a surrogate marker does not significantly impact long term survival outcomes in patients with multiple myeloma in the post-transplant setting and thus should not factor in transplant decision-making. Patients with morbid obesity appear to have a trend towards shortened progression free survival and may warrant further investigation. Figure. Figure. Disclosures Badros: Karyopharm: Research Funding; Celgene: Consultancy, Research Funding; GSK: Research Funding.

Description: Background Despite recent therapeutic advances, multiple myeloma (MM) remains primarily an incurable cancer. Patients experiencing rapid recovery of T cells post autologous stem cell transplant (auto-SCT) may have improved outcomes, and spontaneous cellular responses to tumor can occur, suggesting immune mediated control of tumor is possible. We and others have investigated therapeutic cancer vaccines that have shown promise in pilot studies, in particular following post-transplant infusion of activated autologous T cells. However, efficacy of these approaches may be limited by thymic selection which restricts the repertoire of T cell receptors (TCRs) to low affinity TCRs that cannot recognize the low level of antigen present on most tumor cells. We hypothesized that incorporation of affinity-enhanced tumor antigen-specific TCRs into autologous T cells infused post-transplant would overcome this limitation and improve response rates in the post auto-SCT setting. Methods We report interim results of a Phase II clinical trial (NCT01352286) to evaluate the safety and activity of autologous T cells genetically engineered to express an affinity-enhanced TCR that recognizes the NY-ESO-1/LAGE-1 peptide complex HLA‐A*0201‐SLLMWITQC; these cells are infused in the setting of profound lymphodepletion that accompanies high dose chemotherapy administered during auto-SCT. Patients with high risk or relapsed MM, who are HLA‐A*0201 positive, and whose tumor is positive for NY-ESO-1 and/or LAGE-1 by RT-PCR are eligible. CD25 depleted CD4 and CD8 T cells are activated and expanded using anti-CD3/CD28 antibody conjugated microbeads, and genetically modified with a lentiviral vector containing the TCR construct at a multiplicity of infection of 1. Engineered T cells are administered four days after high dose melphalan and two days following auto-SCT, at a dose range of 1-10 billion total cells with a minimum gene modification requirement of 10%. Patients are evaluated for MM responses in accordance with the IMWG criteria at 6 weeks, and 3 and 6 months post infusion. At 3 months, patients start lenalidomide maintenance. The initial 6 patient phase is complete and a 20 patient extension phase is ongoing. Results Prior to enrollment on study, patients had received a median of 3 prior therapies including 6 with prior transplant. 50% of tumors contained high risk chromosomal abnormalities, and NY-ESO-1 expression is correlated with adverse prognosis. 20 patients (average age of 57) have been infused with an average of 2.3 X 109 engineered T cells (range 4.5 X 108-3.9 X 109); this reflects an average clinical scale transduction efficiency of 34% (range 18% – 49%). Infusions have been well tolerated, and the majority of adverse events were related to the high dose melphalan. Possibly related SAEs were neutropenia and thrombocytopenia, and GI and metabolism disorders including diarrhea, colitis, hyponatremia and hypomagnesemia. 10, 4, 2, and 2 patients have reached the 1 year, 9 month, 6 month and 3 month assessment timepoints, respectively, and 17/20 patients are alive. Best response by day 100 is sCR/CR in 2/15 (13%), nCR in 10/15 (67%), and PR in 3/15% (20%), which compares favorably to historic responses in patients undergoing first or second transplant. Engineered T cells expanded and persisted in blood and marrow at 180 days by Q-PCR and flow-cytometry in all but one case (Figure). 7 patients progressed after day 100, which was accompanied either by loss of engineered T cells or loss of tumor antigen. Detailed phenotyping and functional analysis of engineered T cells, and correlates with clinical responses, is underway. Summary This is the first clinical evaluation of engineered T cells in the MM setting. Infusions are safe, well tolerated, and are associated with encouraging responses in a high risk myeloma population. A study evaluating the engineered T cells in a non-transplant study is underway. Disclosures: Stadtmauer: Celgene: Consultancy. Binder-Scholl:Adaptimmune: Employment. Smethurst:Adaptimmune: Employment. Brewer:Adaptimmune: Employment. Bennett:Adaptimmune: Employment. Gerry:Adaptimmune: Employment. Pumphrey:Adaptimmune: Employment. Tayton-Martin:Adaptimmune: Employment. Ribeiro:Adaptimmune: Employment. Levine:Novartis: cell and gene therapy IP, cell and gene therapy IP Patents & Royalties. Jakobsen:Adaptimmune: Employment. Kalos:Novartis corporation: CART19 technology, CART19 technology Patents & Royalties; Adaptive biotechnologies: Member scientific advisory board , Member scientific advisory board Other. June:Novartis: Patents & Royalties, Research Funding.

Description: BACKGROUND: Immunotherapy in MM is emerging as an effective modality in therapy of MM with the approval of several monoclonal antibodies and encouraging results for vaccines and T cell therapy. Programmed death 1 (PD-1) receptor and its ligand (PD-L1) is one mechanism of immune evasion by MM to suppress T cell function. In this trial, we hypothesized that pembrolizumab, a PD-1-blocking antibody, would enhance immune modulatory properties of pomalidomide in RRMM pts. METHODS: In this single center, phase II study, 48 patients with RRMM received 28-day cycles of pembrolizumab (at a dose of 200 mg IV) every 2 weeks (in a run in phase, first 6 patients received 200 mg IV every 4 weeks) plus pomalidomide (4 mg daily x 21 days) and dexamethasone 40 mg weekly. Study objectives were measurements of safety & efficacy and correlation of the CD3/PD-1 on T cells and PD-L1 on plasma cells with response. RESULTS: The median age was 64 years (range: 35-82); 38% were black and 65% were men, Patients had a median of 3 lines of prior therapy (range: 2-6); All patients had received both IMids and Proteosome inhibitors; 70% had prior auto-SCT. 80% were double refractory to both IMids (lenalidomide) and Proteosome inhibitors [bortezomib (n=18) or carfilzomib (n=20)] and an additional 20% were refractory to lenalidomide. The median time from MM diagnosis to study entry was 4 years (range: 1-25). Most common cytogenetic abnormalities were 1q+ (60%), hyperdiploidy (15%) and high-risk FISH [del 17p, t(4:14) and/or t(14:16)] in 38%. Six patients had soft tissue extramedullary plasmacytomas. There were no infusion-related reactions. Hematologic toxicities (≥ grade 3) were anemia (21%), neutropenia (40%), lymphopenia (15%) and thrombocytopenia (8%). Non-hematologic events Grade ≥3 were fatigue (15%), hyperglycemia (25%), upper respiratory tract infections (21%), rash (10%); and most frequent grade ≥2 were dyspnea (54%), dizziness (44%), increased creatinine 38%, edema (35%), rash (30%), constipation 30%) and arrhythmias (19%). Events of clinical significance, autoimmune mediated, included interstitial pneumonitis (13%), hypothyroidism (10%), transaminitis(6%), adrenal insufficiency (4%) and vitiligo (2%). Nine pts had pomalidomide dose reductions due to rash, neutropenia, palpitations and fatigue; one pt reduced pembrolizumab for pneumonitis. At a median follow up of 10 months (range: 2-18): 25 pts continue on the study and 23 pts discontinued therapy due to disease progression (n= 15), side effects (n=7) and protocol violation (n=1). Five pts died while on study due to progressive disease (n=3), sepsis (n=1, sAE), and one from a cardiac event. Three additional pts died off therapy. On intent to treat analysis; the overall response rate (ORR) with ≥ Partial response were observed in of 27 of 48 pts (56%) including: sCR (n=4, 8%), nCR (n=3, 6%), VGPR (n=6, 13%), PR (n=14, 29%). Additionally, 7 pts (15%) had minimal response, 9 (19%) had stable disease, 2 progressed and 3 were not evaluable for response. Of 38 double refractory pts ORR was 55% including, sCR (n=2, 5%), nCR (n=2, 5%), VGPR (n=4, 10%) and PR (n=13, 27%). Of 18 high-risk pts ORR was 33% including VGPR (n=2, 11%) and PR (n=4, 22%). Median duration of response for responding pts was 8.8 months and for pts ≥ VGPR, DOR was 10.7 months. Correlation of PD-1 and PD-L1 expression and response will be presented. CONCLUSION: Pembrolizumab, pomalidomide and dexamethasone shows promising durable therapeutic activity and an acceptable safety profile in RRMM pts. ClinicalTrials.gov number, NCT02289222 Disclosures No relevant conflicts of interest to declare.