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Long-term outcomes with tafasitamab in R/R DLBCL
tion therapy in the subgroups of patients with primary refractory, rituximab-refractory and last-therapy-refracto- ry disease, especially given that these patients are consid- ered difficult to treat, and those responses were durable. The median PFS and OS were, however, shorter than those for the overall population, especially in primary refractory patients, so there is still room for improvement in outcomes for difficult-to-treat patients. Notably, two patients with double- and triple-hit lymphoma and seven out of eight patients with transformed lymphoma responded to therapy.
In the exploratory subgroup analysis, the only disease characteristic that appeared to have a negative effect on prognosis was IPI score ≥3 (i.e., intermediate-high- or high-risk disease); a high IPI score has long been recog- nized as a risk factor for poor outcomes in DLBCL.14
In regard to safety, there was little change in the adverse event profile since the primary analysis, which indicates a good tolerability profile for tafasitamab monotherapy. There was a reduction in the burden of common hematologic and non-hematologic adverse events as patients transitioned from combination therapy to tafasitamab monotherapy, with a residual tolerability profile similar to that in previous studies of tafasitamab monotherapy.10,11 This observation is of considerable importance for frail or elderly patients, who may prefer treatment with limited effects on their quality of life. In particular, the low incidence of infusion-related reactions (all of which were grade 1) and absence of cytokine release syndrome with tafasitamab plus lenalidomide is an important consideration for therapy in frail patients, given the occurrence of these events with CAR T-cell and other antibody therapies.
Subsequent treatment, including ASCT and CAR T cells, was not precluded by previous administration of tafasitamab and lenalidomide in patients who experi- enced disease progression during this combination regi- men.
In this trial, lenalidomide was given for a limited time of up to 12 months, which is in line with the median DoR of lenalidomide monotherapy in R/R non-Hodgkin lym- phoma of 10.5 months,15,16 and the observation that the best responses with tafasitamab plus lenalidomide typi- cally occur within this time window. Treatment until pro- gression with tafasitamab is a novel concept, and although the exact contribution of the monotherapy phase cannot be delineated in this trial, it deserves further investigation. The excellent durability of CR achieved raises the question of whether cure is possible with tafa- sitamab plus lenalidomide; longer follow-up data will be needed to assess this.
Patients with R/R DLBCL who are not eligible for ASCT have few options. In patients who had previously received rituximab, cytotoxic chemotherapy with six to eight cycles of rituximab plus gemcitabine and oxaliplatin was associated with a CR/unconfirmed CR rate of 42% with a median PFS of 4 months and median OS of 8 months, and an overall high incidence of grade ≥3 neu- tropenia (73%) and thrombocytopenia (44%), requiring transfusions of blood (33%) and platelets (23%).17
In patients with third- or later-line disease, the median PFS of 7.6 months and median OS of 15.5 months with tafasitamab plus lenalidomide are comparable with those achieved with other options such as polatuzumab plus bendamustine and rituxiamb (approved for R/R DLBCL
in the European Union)7 and CAR T-cell therapy.6,18 The median DoR has not been reached, with more than 80% of patients with a best response of CR still in remission after 3.5 years. The L-MIND regimen is readily available to administer in an outpatient setting, with oral lenalido- mide self-administered by the patient and weekly tafa- sitamab infusions (fortnightly after the first 3 months of therapy).
In conclusion, combination therapy with tafasitamab plus lenalidomide followed by tafasitamab monotherapy provided clinically significant durable responses in patients with R/R DLBCL who were not eligible for ASCT, including those with refractory disease, with man- ageable toxicity during combination treatment and a reduced adverse event burden during tafasitamab monotherapy. These long-term data further validate tafa- sitamab plus lenalidomide followed by extended tafasita- mab monotherapy as a valuable option for patients with R/R DLBCL who are not eligible for ASCT.
Disclosures
EGB reports receiving personal fees for consultancy from Janssen, Gilead, Sandoz, Celltrion, and Celgene, and honoraria from Roche, Janssen, AbbVie, and Takeda. GG reports receiving personal fees for advisory board participation from AbbVie, Janssen, AstraZeneca, and Sunesys, and for participation in a speaker bureau from AbbVie and Janssen. GS reports receiving personal fees for consultancy from Epizyme and Ipsen; advisory board participation or symposia from MorphoSys, AbbVie, BeiGene, Genmab, Velosbio, Celgene/BMS, Incyte, Janssen, Novartis, Gilead/Kite, and Genentech/Roche outside the submit- ted work; and has a patent issued (WO2012010561A1: char- acterization of another anti-CD19 monoclonal antibody with antibody-dependent cell-mediated cytotoxicity, developed in col- laboration with IDD-biotech); this antibody and the company has no relationship with the anti-CD19 antibody described in the current paper (tafasitamab) and has not been licensed to any third party. KM reports receiving personal fees for advisory board participation from MorphoSys during the conduct of the study, and from Pharmacyclics, BMS, Celgene, Kite, and Seattle Genetics outside the submitted work. MD reports receiving an institutional research grant from AbbVie, Bayer, Celgene, Janssen, and Roche; personal fees for advisory board participa- tion from AstraZeneca, Bayer, BeiGene, Celgene, Genmab, Gilead, Incyte, Janssen, Novartis, and Roche; and speaker fees fromAmgen,AstraZeneca,Bayer,Celgene,Gilead,Janssen,and Roche, all outside the submitted work. NK reports receiving research funding from Celgene, outside the submitted work. OT reports receiving personal fees from Roche, Gilead, AbbVie, Celgene, Janssen, Sandoz and iQuone, and travel grants from Roche, Gilead, AbbVie, Celgene and Janssen outside the submit- ted work. WJ reports receiving research funding from MorphoSys during the conduct of the study, and Roche, Sandoz and Celltrion outside the submitted work. AO reports honoraria from Roche and personal fees for advisory board participation from Janssen. JW, MDH, and SA are employees of MorphoSys AG, Planegg, Germany. All other authors declare no competing interests.
Contributions
JD, GS, JW, MD-H, and SA analyzed and interpreted the data. All authors contributed to data acquisition, manuscript development, and approval. All authors interpreted the results and agree on accountability for all study aspects, including accu- racy, integrity, and protocol adherence. All authors contributed to study design or conduct, data analyses, or manuscript writing.
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