Kurzfassung: Introduction Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT) have a poor prognosis. Tafasitamab (MOR208) is an Fc-enhanced, humanized, monoclonal antibody that targets CD19, which is broadly expressed across B-cell malignancies, including DLBCL. Lenalidomide (LEN) is an immunomodulatory drug with antiproliferative and antiangiogenic effects. Combined tafasitamab + LEN has shown enhanced activity in in vitro and in vivo lymphoma models. L-MIND (NCT02399085) is an ongoing, open-label, single-arm, Phase II study of tafasitamab + LEN in patients with R/R DLBCL who are ineligible for ASCT. Here, we present results from prespecified patient subgroup analyses from L-MIND. Methods Patients aged ≥18 years with R/R DLBCL (1-3 prior systemic therapies, including ≥1 CD20-targeting regimen) with an Eastern Cooperative Oncology Group performance status 0-2, and who were ineligible for ASCT were enrolled. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during Cycles 1-3 with a loading dose on Cycle 1 Day 4, then every 2 weeks during Cycles 4-12. LEN (25 mg orally) was administered on Days 1-21 of Cycles 1-12. After Cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint is objective response rate (ORR; partial response [PR] + complete response [CR] ), assessed centrally by an independent review committee (IRC) per International Working Group criteria 2007, incorporating PET-based imaging. Secondary endpoints include ORR (investigator-assessed), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and biomarker analyses. Results Of 81 patients enrolled, 80 patients received tafasitamab + LEN and were included in the full analysis set (FAS) for efficacy (data cut-off 30 Nov 2018). Median follow-up was 17.3 months. In the FAS, ORR was 60.0% (95% confidence interval [CI]: 48.4-70.8) (Figure 1A). The CR rate was 42.5% (n=34/80), of which 88.2% (n=30/34) were PET-confirmed. Median time to response (PR or CR) was 2.0 months and median time to CR was 7.1 months. Median DOR was 21.7 months (95% CI: 21.7-not reached [NR] ); median PFS was 12.1 months (95% CI: 5.7-NR); and median OS was NR (95% CI: 18.3-NR) with a median follow-up of 19.6 months. The 12-month DOR and OS rates were 71.6% (95% CI: 55.1-82.9) (Figure 1B) and 73.7% (95% CI: 62.2-82.2) (Figure 1C), respectively. In the subgroup analysis, patients with CR as best objective response (BOR) had better outcomes than those with PR: median DOR, NR (95% CI: 21.7-NR) vs 4.4 months (95% CI: 2.0-9.1); 12-month DOR rate, 93.2% (95% CI: 75.4-98.3) vs 14.4% (95% CI: 1.1-43.7); and 12-month OS rate, 97.1% vs 76.9%. Patients with one prior line of therapy had a trend for better outcomes than those with ≥2 prior lines: ORR, 70.0% vs 50.0%; and 12-month OS rate, 86.9% vs 60.1%. However, the 12-month DOR rate was similar regardless of the number of prior lines (one prior line: 70.5% [95% CI: 47.2-85.0] vs ≥2 prior lines: 72.7% [95% CI: 46.3-87.6] ). For patients who were refractory to primary therapy or their last line of therapy, similar ORRs were observed to non-refractory patients (60.0% vs 60.0%); 12-month DOR was similar regardless of refractory status to last therapy; and 12-month OS rates were higher in non-refractory patients (Figure 1C). As expected, patients with a low/low-intermediate International Prognostic Index (IPI) score had better outcomes than those with an intermediate-high/high score: ORR, 70.0% vs 50.0%; 12-month DOR rate, 86.5% vs 50.4%; and 12-month OS rate, 87.0% vs 59.9%. Based on Hans algorithm, encouraging outcomes were reported in patients with germinal center B-cell (GCB) DLBCL (n=37), and outcomes were even better in those with non-GCB DLBCL (n=21): ORR, 48.6% vs 71.4%; median DOR, NR vs 21.7 months; 12-month DOR rate, 53.5% vs 83.1%; and 12-month OS rate, 65.4% vs 84.2%. Conclusions Tafasitamab + LEN combination followed by tafasitamab monotherapy shows encouraging activity with durable responses in ASCT-ineligible patients with R/R DLBCL. L-MIND includes a substantial number of poor prognosis patient subgroups. While the influence of these risk factors is evident, the clinical activity of tafasitamab + LEN in these difficult-to-treat patients is promising, particularly in those who were refractory to prior therapies. Disclosures Duell: Regeneron Pharmaceuticals, Inc.: Research Funding. Maddocks:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Merck: Research Funding; BMS: Research Funding. González-Barca:Janssen: Consultancy, Honoraria; Kiowa: Consultancy; Celtrion: Consultancy; Celgene: Consultancy; AbbVie: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Honoraria. Jurczak:TG Therapeutics: Research Funding; Roche: Research Funding; Takeda: Research Funding; Servier: Research Funding; Celtrion: Research Funding; Novo Nordisk: Research Funding; Incyte: Research Funding; Bayer: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding. Liberati:Incyte: Consultancy; Janssen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol & Mayer: Honoraria. de Vos:Bayer: Consultancy; Verastem: Consultancy; Portola Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Nagy:Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Gaidano:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sunesys: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Abrisqueta:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau. André:Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers-Squibb: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel grants, Research Funding; Amgen: Other: Travel grants, Research Funding; Johnson & Johnson: Research Funding; Takeda Millenium: Research Funding; Chugai: Research Funding; Celgene: Other: Travel grants, Research Funding. Dreyling:Celgene: Other: Scientific advisory board, Research Funding, Speakers Bureau; Gilead: Other: Scientific advisory board, Speakers Bureau; Janssen: Other: Scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Other: Scientific advisory board, Research Funding; Novartis: Other: Scientific advisory board; Roche: Other: Scientific advisory board, Research Funding, Speakers Bureau; Sandoz: Other: Scientific advisory board; Acerta: Other: Scientific advisory board; Bayer: Other: Scientific advisory board, Speakers Bureau. Menne:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyowa Kirin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grant, Research Funding, Speakers Bureau. Dirnberger-Hertweck:MorphoSys: Employment. Weirather:MorphoSys: Employment. Ambarkhane:MorphoSys: Employment. Salles:Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Epizyme: Consultancy, Honoraria; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria.

Kurzfassung: Introduction Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT) have a poor prognosis. Tafasitamab (MOR208) is an Fc-enhanced, humanized, monoclonal antibody that targets CD19, which is broadly expressed across B-cell malignancies, including DLBCL. The immunomodulatory drug lenalidomide (LEN) has antiproliferative and antiangiogenic effects. L-MIND (NCT02399085) is an ongoing, open-label, single-arm, Phase II study of tafasitamab + LEN in patients with R/R DLBCL who are ineligible for ASCT. L-MIND results from prespecified patient subgroup analyses were presented previously (primary analysis: data cut-off Nov 30, 2018). Here, we report long-term clinical efficacy from the L-MIND study after a median follow-up of 31.8 months for overall survival (OS) (data cut-off: Nov 30, 2019). Methods Patients enrolled were aged ≥18 years with R/R DLBCL (1-3 prior systemic therapies, including ≥1 CD20-targeting regimen), ASCT-ineligible and with an Eastern Cooperative Oncology Group performance status of 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during Cycles 1-3 with a loading dose on Cycle 1 Day 4, then every 2 weeks during Cycles 4-12. LEN (25 mg orally) was administered on Days 1-21 of Cycles 1-12. After Cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint is objective response rate (ORR; partial response [PR] + complete response [CR] ), assessed centrally by an independent review committee. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), OS and safety analyses. Results Of 81 patients enrolled, 80 patients received tafasitamab + LEN and were included in the full analysis set (FAS) for efficacy. Median follow-up was 22.7 months. In the FAS, ORR was 57.5% (95% confidence interval [CI]: 45.9-68.5) (Figure 1A). The CR rate was 40.0% (n=32/80), of which 90.6% (n=29/32) were PET-confirmed. Median time to response (PR or CR) was 2.0 months and median time to CR was 6.1 months. Median DOR was 34.6 months (95% CI: 26.1-34.6); median PFS was 12.1 months (95% CI: 6.3-not reached [NR] ); and median OS was 31.6 months (95% CI: 18.3-NR). The 24-month DOR and OS rates were 71.3% (95% CI: 52.8-83.7) (Figure 1B) and 57.2% (95% CI: 45.1-67.5) (Figure 1C), respectively. In the subgroup analysis, patients with CR as best objective response had better outcomes than those with PR: median DOR, NR (95% CI: 26.1-NR) vs 5.6 months (95% CI: 2.2-34.6); 24-month DOR rate, 86.4% (95% CI: 61.3-95.7) vs 38.5% (95% CI: 14.1-62.8); and 24-month OS rate, 90.6% vs 42.7%. Patients with 1 prior line of therapy had a trend for better outcomes than those with ≥2 prior lines: ORR, 67.5% vs 47.5%; 24-month OS rate, 67.9% vs 46.3%. The 24-month DOR rate was similar by the number of prior lines (1 prior line: 67.9% [95% CI: 42.5-84.0] vs ≥2 prior lines: 77.8% [95% CI: 51.1-91.0] ). ORR was similar by primary refractory vs non-primary refractory status (53.3% vs 58.5%); however, primary refractory status impacted 24-month DOR (50.0% vs 74.8%, respectively). Patients refractory to their last line of therapy achieved similar ORRs to those who were not (60.0% vs 55.6%). The 24-month DOR was similar regardless of refractory status to last therapy (Figure 1B), and 24-month OS rates were higher in non-refractory patients (Figure 1C). As expected, patients with a low/low-intermediate International Prognostic Index score had better outcomes than those with an intermediate-high/high score: ORR, 67.5% vs 47.5%; 24-month DOR rate, 92.1% vs 44.3%; and 24-month OS rate, 76.5% vs 36.5%. Based on the Hans algorithm, outcomes were encouraging independent of germinal center B-cell (GCB) DLBCL (n=38) or non-GCB DLBCL (n=22) disease: ORR, 47.4% vs 68.2%; median DOR, 34.6 vs 26.1 months; 24-month DOR rate, 66.7% vs 62.9%; and 24-month OS rate, 51.3% vs 65.0%. Conclusions Long-term L-MIND subgroup data show that encouraging activity observed at primary analysis remains durable after ≥2 years of follow-up; patients with CR continue to experience long DOR and high OS. Although the influence of poor prognosis risk factors is still evident, the clinical activity of tafasitamab in combination with LEN followed by tafasitamab monotherapy continues to show promise in difficult-to-treat ASCT-ineligible patients with R/R DLBCL. Disclosures Maddocks: Pharmacyclics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Consultancy; ADC Therapeutics, AstraZeneca: Consultancy; BMS: Consultancy, Research Funding; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Duell:Morphosys: Research Funding. González-Barca:Sandoz: Consultancy; Gilead: Consultancy; Janssen: Consultancy, Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Roche: Honoraria; MorphoSys: Other; Celtrion: Consultancy; Kiowa: Consultancy; Celgene: Consultancy. Jurczak:Janssen, MeiPharma, Merck, Pharmacyclics, Roche, Tekeda, TG Therapeutics: Research Funding; Jagiellonian University: Ended employment in the past 24 months, Research Funding; Maria Sklodowska-Curie National Research Institute of Oncology: Consultancy, Current Employment. Liberati:Novartis: Research Funding; GSK: Research Funding; Incyte: Honoraria; Janssen: Honoraria, Research Funding; Oncopeptides: Research Funding; Morphosys: Research Funding; Karyopharm: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Research Funding; Onconova: Research Funding; Verastem: Research Funding. de Vos:Bayer: Consultancy; Verastem: Consultancy. Nagy:MorphoSys AG: Patents & Royalties. Obr:Roche: Honoraria. Gaidano:Sunesys: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Membership on an entity's Board of Directors or advisory committees. Abrisqueta:Roche: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau. André:Celgene: Other, Research Funding; Johnson & Johnson: Research Funding; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy; Novartis: Consultancy, Research Funding; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Takeda: Consultancy; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment. Dreyling:Celgene: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Abbvie: Research Funding; Astra Zeneca: Consultancy; Beigene: Consultancy; Gilead: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau. Menne:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Other: Travel costs, Speakers Bureau; Pfizer: Honoraria, Other: Travel costs, Speakers Bureau; Celgene: Honoraria, Other: Travel grants; Roche: Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Astra Zeneca: Research Funding; Takeda: Honoraria, Speakers Bureau. Dirnberger-Hertweck:MorphoSys AG: Current Employment. Weirather:MorphoSys AG: Current Employment. Ambarkhane:MorphoSys AG: Current Employment. Salles:Takeda: Honoraria; BMS/Celgene: Honoraria, Other: consultancy or advisory role; Autolos: Other: consultancy or advisory role; Abbvie: Other: consultancy or advisory role; Roche: Honoraria, Other: consultancy or advisory role; Novartis: Honoraria, Other: consultancy or advisory role; MorphoSys: Honoraria, Other: consultancy or advisory role; Janssen: Honoraria, Other: consultancy or advisory role; Epizyme: Honoraria, Other: consultancy or advisory role; Kite, a Gilead Company: Honoraria, Other: consultancy or advisory role ; Debiopharm: Consultancy, Honoraria, Other: consultancy or advisory role; Genmab: Honoraria, Other; Karyopharm: Honoraria.

Kurzfassung: Tafasitamab (MOR208), an Fc-modified, humanized, anti-CD19 monoclonal antibody, combined with the immunomodulatory drug lenalidomide was clinically active with a good tolerability profile in the open-label, single-arm, phase II L-MIND study of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem-cell transplantation. To assess long-term outcomes, we report an updated analysis with ≥35 months’ follow-up. Patients were aged 〉 18 years, had received one to three prior systemic therapies (including ≥1 CD20-targeting regimen) and Eastern Cooperative Oncology Group performance status 0-2. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during cycles 1-3, then every 2 weeks during cycles 4-12. Lenalidomide (25 mg orally) was administered on days 1-21 of cycles 1-12. After cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was best objective response rate. After ≥35 months’ follow-up (data cut-off: October 30, 2020), the objective response rate was 57.5% (n=46/80), including a complete response in 40.0% of patients (n=32/80) and a partial response in 17.5% of patients (n=14/80). The median duration of response was 43.9 months (95% confidence interval [95% CI]: 26.1-not reached), the median overall survival was 33.5 months (95% CI: 18.3-not reached) and the median progression-free survival was 11.6 months (95% CI: 6.3-45.7). There were no unexpected toxicities. Subgroup analyses revealed consistent long-term efficacy results across most subgroups of patients. This extended follow-up of L-MIND confirms the long duration of response, meaningful overall survival, and well-defined safety profile of tafasitamab plus lenalidomide followed by tafasitamab monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplantation. ClinicalTrials.gov identifier: NCT02399085.

Kurzfassung: Introduction: The CD19 antigen is broadly and homogeneously expressed across different B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL). MOR208 is an Fc-enhanced, humanized, monoclonal antibody that targets CD19, leading to natural killer (NK) cell-mediated antibody-dependent cytotoxicity, macrophage-mediated antibody-dependent phagocytosis and direct cytotoxicity. The immunomodulatory drug, lenalidomide (LEN), has both antiproliferative and antiangiogenic effects, and can stimulate the activity of immune effectors, such as NK cells. MOR208 and LEN have each shown single agent activity in patients with relapsed or refractory (R-R) DLBCL. In addition, MOR208 and LEN have shown synergy in in vitro and in vivo lymphoma models. We present results of an ongoing, multicenter phase II study designed to assess the safety and efficacy of MOR208 combined with LEN in patients with R-R DLBCL (NCT02399085). Methods:Patients 〉 18 years of age diagnosed with DLBCL, an Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function, who had relapsed after or were refractory to at least one but not more than three prior systemic therapies, including at least one CD20-targeting regimen, and who were not candidates for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT), were eligible. Patients with primary refractory disease (defined as no response to or progression during or within 6 months after completion of frontline therapy for DLBCL) were excluded. Treatment comprises up to twelve 28-day cycles of MOR208, administered intravenously at a dose of 12 mg/kg weekly during cycles 1-3 (plus a loading dose on day 4 of cycle 1), and every second week during cycles 4-12. LEN was administered orally at a daily dose of 25 mg on days 1-21 of each cycle, for up to 12 cycles. Patients who were progression-free after 12 cycles received MOR208 every second week until progression. The primary endpoint is the objective response rate (ORR), centrally assessed, as per the International Working Group criteria 2007, incorporating PET-based imaging. Secondary endpoints include ORR as per investigator assessment, duration of response (DoR), progression-free survival (PFS) and overall survival (OS), safety, and analysis of outcomes by cell of origin and other biomarkers. Results: As of November 2017, 81 patients had been enrolled and recruitment is complete. We report here updated preliminary results with a data cutoff of 5 June 2018. Median age was 72 years (range 41-87); 40 (49%) patients had received ≥2 prior lines of therapy (median 2, range 1-4); 31 (38%) had rituximab refractory disease; 33 (41%) were refractory to the previous line of therapy, 43 (53%) had Ann Arbor stage ≥III disease; and 42 (52%) had an International Prognostic Index of 3-5 at study entry, indicating poor prognosis. The most common treatment-emergent adverse events (any grade/grade ≥3) were neutropenia in 39/35 (48%/43%) patients, thrombocytopenia in 26/14 (32%/17%), anemia in 25/7 (31%/9%), diarrhea in 24/1 (30%/1%), pyrexia in 18/1 (22%/1%) and asthenia in 16/2 (20%/2%) patients. Thirty-four (42%) patients required dose reduction with LEN, 58 (72%) patients overall could stay on a daily LEN dose of 20 mg or higher. Based on investigator assessments, complete and partial responses were observed in 27 (33%) and 20 (25%) patients, respectively, resulting in an ORR of 58%. A further 12 (15%) patients had stable disease. With a median follow-up of 12 months, the median PFS was 16.2 months (95% CI: 6.3-not reached [NR] ). Responses were durable with a median DoR not reached (95% CI: NR-NR) and 70% of responding patients were without progression at 12 months (Kaplan-Meier estimate). A significant proportion of patients (37/81; 46%) are still on study treatment, with 19 having been treated for over 12 months. Median OS has not been reached (95% CI: 18.6-NR); the 12-month OS rate was 73% (95% CI: 63-85). Conclusions: MOR208 in combination with LEN has shown highly encouraging activity in patients with R-R DLBCL who were ineligible for HDC and ASCT and who had a poor prognosis. These results indicate a significant improvement in outcome for these patients who have very limited treatment options. MOR208 plus LEN was well tolerated in this population, without evidence of additive toxicity. Treatment and follow-up are currently ongoing, as are cell of origin and other biomarker analyses. Disclosures Salles: Novartis: Consultancy, Honoraria; Epizyme: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Merck: Honoraria; Morphosys: Honoraria; Pfizer: Honoraria; Servier: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Acerta: Honoraria; AbbVie: Honoraria; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding. González-Barca:Roche: Speakers Bureau; Celtrion: Consultancy; Gilead: Consultancy; janssen: Consultancy, Speakers Bureau. Jurczak:Pharmacyclics: Research Funding; MorphoSys: Research Funding; Merck: Research Funding; Nordic Nanovector: Research Funding; Janssen: Research Funding; Epizyme: Research Funding; Celgene: Research Funding; Beigene: Research Funding; Bayer: Research Funding; Afimed: Research Funding; Sandoz-Novartis: Consultancy; Janssen: Consultancy; European Medicines Agency: Consultancy; AstraZeneca: Consultancy; Acerta: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Servier: Research Funding; Roche: Research Funding; TG Therapeutics: Research Funding. Gaidano:Morphosys: Honoraria; AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Kalakonda:Celgene: Research Funding. Dreyling:Bayer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Acerta: Consultancy; Roche: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sandoz: Consultancy. Zinzani:Janssen: Honoraria, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dirnberger-Hertweck:MorphoSys: Employment. Weirather:MorphoSys: Employment. Ambarkhane:MorphoSys: Employment. Maddocks:Pharmacyclics: Research Funding; Novartis: Research Funding; Pharmacyclics/Janssen: Honoraria; AstraZeneca: Honoraria; Teva: Honoraria; Merck: Research Funding; BMS: Research Funding.

Kurzfassung: Background: CD19 is broadly and homogeneously expressed across different B-cell malignancies and represents an attractive target antigen in patients with B-cell non-Hodgkin's lymphoma (NHL). Tafasitamab (MOR208) is an Fc-enhanced, humanized, anti-CD19 monoclonal antibody. This ongoing study is investigating the single agent antitumor activity in adult patients with relapsed or refractory (r/r) NHL who had received at least one prior rituximab-containing therapy. Patients and Methods: The study enrolled 92 r/r NHL patients: diffuse large B-cell lymphoma (DLBCL; n=35), mantle cell lymphoma (MCL; n=12), follicular lymphoma (FL; n=34), or other indolent NHL (iNHL; n=11). The median number of prior systemic therapies was three (range 1-15) for the entire patient population. The primary efficacy endpoint was investigator-assessed overall response rate (ORR) based on the revised International Working Group Response Criteria (Cheson et al., et al. J Clin Oncol 2007). Secondary objectives were to evaluate the time-to-response, duration of response (DoR), time to progression and progression-free survival (PFS), and to establish the safety and tolerability of tafasitamab. Patients received up to three 28-day cycles with weekly infusions of 12 mg/kg body weight of tafasitamab. Premedication, including antipyretics, histamine H1 receptor blockers and glucocorticosteroids, was administered for the first three infusions. Patients with ongoing at least partial remission (PR) at the end of Cycle 3 received further tafasitamab treatment until disease progression, either monthly or every second week. Results: The investigator-assessed best response (intent-to-treat analysis) in the different subgroups at cut-off date (28 Sep 2018) is shown in Table 1. Five patients in complete remission (CR) (one DLBCL, two FL, two other iNHL) were ongoing and still on tafasitamab treatment at the cut-off date. These patients were on treatment for more than 4 years. The median DoR was 20.1 months in DLBCL and 24 months in FL (Table 2). The median PFS was 2.7 (95% confidence interval [CI] 2.1-13.2 months) and 6.6 months (95% CI 5.3-20.5 months) in DLBCL and FL, respectively. The PFS rate at 12 months was 34.3% and 39.2% for DLBCL and FL, respectively (Table 2). Similar PFS was observed in rituximab-refractory as well as non-refractory patients. Patients with a peripheral blood natural killer (NK) cell count 〉 100 cells/µL at baseline had a median PFS of 4.2 months (DLBCL) or 8.8 months (FL/iNHL), as compared with patients who had 〈 100 NK cells/µL at baseline showing a median PFS of 2.1 months (DLBCL) or 3.2 months (FL/iNHL), respectively. Tafasitamab was well tolerated in patients with r/r NHL. Most treatment-emergent adverse events (TEAEs) were mild in nature. The most common grade ≥3 TEAEs were neutropenia (9.8%), thrombocytopenia (4.3%), anemia (3.3%) and pneumonia (3.3%). Four patients (4.3%) experienced serious adverse reactions (febrile neutropenia, genital herpes zoster, infusion-related reaction and myelodysplastic syndrome). There was no evidence of grade ≥3 late toxicity during the long-term follow-up period; no treatment-related deaths occurred. Conclusion: Tafasitamab monotherapy until progression resulted in durable responses and was well tolerated in patients with both aggressive and indolent NHL subtypes. Disclosures Jurczak: Celgene: Research Funding; Bayer: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Servier: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Roche: Research Funding; MorphoSys: Research Funding; Celtrion: Research Funding; Gilead: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Incyte: Research Funding. Zinzani:Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Hess:Janssen: Consultancy, Honoraria, Other: personal fees; Celgene: Consultancy, Employment, Honoraria, Other: personal fees, Research Funding; Roche: Consultancy, Employment, Honoraria, Other: personal fees, Research Funding; Pfizer: Other: personal fees, Research Funding; CTI: Consultancy, Employment, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria. Gaidano:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra-Zeneca: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sunesys: Consultancy, Honoraria. Provencio:Takeda: Consultancy, Other: Travel, accommodation and expenses, Speakers Bureau; Novartis: Consultancy, Other: Travel, accommodation and expenses, Speakers Bureau; AstraZeneca: Consultancy, Other: Travel, accommodation and expenses, Speakers Bureau; Pierre Fabre: Consultancy, Other: Travel, accommodation and expenses, Speakers Bureau; Boehringer Ingelheim: Consultancy, Other: Travel, accommodation and expenses, Research Funding, Speakers Bureau; Roche: Consultancy, Other: Travel, accommodation and expenses, Research Funding, Speakers Bureau; BMS: Consultancy, Other: Travel, accommodation and expenses, Speakers Bureau; MSD: Consultancy, Other: Travel, accommodation and expenses, Speakers Bureau. Nagy:Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Robak:Morphosys AG: Research Funding; BeiGene: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel grant, Research Funding; Gilead: Consultancy, Research Funding; Acerta: Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grant, Research Funding; Amgen: Consultancy, Other: Travel grant; Roche: Consultancy, Other: Travel grant, Research Funding; Takeda: Consultancy, Research Funding; UCB: Honoraria, Research Funding. Maddocks:Teva: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Buske:Amgen: Research Funding; Bayer: Research Funding; Roche: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria; Celltrion: Honoraria, Speakers Bureau; Hexal: Honoraria, Speakers Bureau. Ambarkhane:MorphoSys: Employment. Brugger:MorphoSys: Employment; AstraZeneca: Equity Ownership. Dirnberger-Hertweck:MorphoSys: Employment. Tillmanns:MorphoSys AG: Employment. Weirather:MorphoSys: Employment.