Nearly two-thirds of patients with newly diagnosed DLBCL are cured with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy. A minority of those with relapsed disease are candidates for salvage chemotherapy followed by high dose therapy and autologous stem cell transplant (ASCT), however few attain long-term remission. Moreover, those with refractory disease have a median survival of 6 months, which presents a dire need for improved treatments in patients with this deadly presentation.
The emergence of new targeted agents and immunotherapies represents a sea change in the treatment landscape for B-cell lymphomas. Approvals of CAR T-cell therapy, the anti-CD19 monoclonal antibody tafasitamab (Monjuvi), and the antibody-drug conjugate polatuzumab (Polivy) now bring effective treatment options to those with relapsed/refractory disease. Tafasitamab is an Fc-enhanced, anti-CD19 monoclonal antibody that has exhibited single-agent activity in patients with relapsed or refractory B-cell malignancies. It is suggested to act synergistically with lenalidomide (Revlimid), and the immunotherapy dyad of tafasitamab and lenalidomide became the first FDA-approved therapy as second-line treatment of DLBCL. In the Phase II L-MIND study, 80 patients with relapsed/refractory DLBCL who were unsuitable for ASCT, attained an overall response rate (ORR) of 60%, and 43% of patients attained a complete response with a median duration of response 21.7 months and a median progression-free survival (PFS) of 12.1 months. Notably, median overall survival (OS) was not reached. Researchers observed responses in patients with both germinal center and nongerminal center DLBCL and the combination was found to be well tolerated.
What are your experiences with these novel treatments for DLBCL?
How do you advise your patients on prognosis and other concerns related to these novel treatments?
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M MerrickJuly 03, 2021Tafasitamab plus lenalidomide in L-MIND study as reported in Lancet appears promising and may be option for patients not candidates for ASCT/ CAR T
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Prabhsimranjot SinghJuly 02, 2021Interesting and happy we have newer and novel therapies emerging, now the BIG question will be sequencing the treatments and assess how to achieve the most efficacious pathway, will one treatment works as good in second line as in third line and most importantly what will be the response of Monjuviafter ASCT and or CAR-T?
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DLBCL ConnectJuly 02, 2021What are your thoughts on the Phase II L-MIND study? Please share.
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David Vesole, Regional Cancer Care AssociatesJuly 01, 2021I would still go with a either a CAR T cell or autologous transplant for patients with chemotherapy sensitive disease to salvage therapy-these modalities have definite cure rates. The major forthcoming debate is CAR T cell OR autotransplant as a recent head to head showed an advantage for CAR T cells-this data needs to mature but looks quite promising. Both of these modalities are one and done and do not require repetitive dosing nor the long term risk of toxicities which may occur with any of the other new modalities.
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Parth RaoJuly 01, 2021For R/R DLBCL, after 2 lines of therapy- preference is CAR-T if they are eligible. if they are not, i usually prefer monjuvi/len combination since majority of these cases are chemorefractory and this combination comes in with a different MOA. If POD on monjuvi/len, then Polivy BR. In addition, Polivy BR combination- the response rates on GC subtype was lower and PFS was shorter ( not powered, but post hoc data)
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Sherif BadawyJuly 01, 2021I think all recent novel therapies for relapsed/refractory DLBCL, including CAR-T, Polivy, and Monjuvi are very promising. Response rate is good with favorable safety profiles. I think taking a patient-centered approach is key to discuss each treatment option and review what we know about each product and/or strategy from clinical trial data.
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Ali MirmiranJuly 01, 2021My experience with CART, Polivy, and Monjuvi in r/r DLBCL has been good thus far. The response rates have been high, and the toxicities have been consistent with the reported incidences. I advise my patients of the expected efficacy rates and risks of adverse events.
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Edmund Waller, THE EMORY CLINIC INCJune 22, 2021The recent press release reported that the Juno-sponsored study randomizing DLBCL patients at first relapse to CART versus salvage RICE was positive in favor of superior EFS in the CART arm. This needs to be examined closely for the durability of CR in CART-treated patients. If CART is indeed curative, other salvage therapies that are palliative will be less attractive in this setting.
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Keith Shulman, ONCOLOGY OF NORTHSHORE CLINIC INCJune 22, 2021Tafasitamab seems like it has more activity than thevother agents so may be preferred as second line, but i dont have experience with it to know for sure.
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Mark FeslerMay 07, 2021Hi Kumar. We have 2 of the 3 car T. Will have 3rd later this year. Factors in deciding for DLbCL are rates of NT, manufacturing speed and success. Some indications like mantle cell have only 1 approved. Hardest decision is what to do with deauville 4 or PRs to 2nd line chemo ...car vs auto
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Mark FeslerMay 07, 2021Hi Kumar. We have 2 of the 3 car T. Will have 3rd later this year. Factors in deciding for DLbCL are rates of NT, manufacturing speed and success. Some indications like mantle cell have only 1 approved. Hardest decision is what to do with deauville 4 or PRs to 2nd line chemo ...car vs auto
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Mark FeslerMay 07, 2021Hi Kumar. We have 2 of the 3 car T. Will have 3rd later this year. Factors in deciding for DLbCL are rates of NT, manufacturing speed and success. Some indications like mantle cell have only 1 approved. Hardest decision is what to do with deauville 4 or PRs to 2nd line chemo ...car vs auto
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Kumar AbhishekMay 05, 2021@ Mark, are you doing CAR-T at SLU. Do you have access to all CAR-T and how do you decide between various options at least in DLBCL?
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Kumar AbhishekMay 05, 2021@ Mark, are you doing CAR-T at SLU. Do you have access to all CAR-T and how do you decide between various options at least in DLBCL?
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Kumar AbhishekMay 05, 2021@ Mark, are you doing CAR-T at SLU. Do you have access to all CAR-T and how do you decide between various options at least in DLBCL?
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Kumar AbhishekMay 05, 2021I have treated transplant and CAR T ineligible patients with Polivy+BR in third line and Tafa/Len in 2nd , 3rd and 4th line. I am pleased with the responses of these agents. I am yet to see durable response beyond 6 months. However I remain hopeful. These drugs are well tolerated but cytopenias can be a challenging issue. I tell patients that broadly speaking 4/10 would respond to therapy and mPFS remain in the range of about 6 months. These are not curative treatments.
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Kumar AbhishekMay 05, 2021I have treated transplant and CAR T ineligible patients with Polivy+BR in third line and Tafa/Len in 2nd , 3rd and 4th line. I am pleased with the responses of these agents. I am yet to see durable response beyond 6 months. However I remain hopeful. These drugs are well tolerated but cytopenias can be a challenging issue. I tell patients that broadly speaking 4/10 would respond to therapy and mPFS remain in the range of about 6 months. These are not curative treatments.
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Kumar AbhishekMay 05, 2021I have treated transplant and CAR T ineligible patients with Polivy+BR in third line and Tafa/Len in 2nd , 3rd and 4th line. I am pleased with the responses of these agents. I am yet to see durable response beyond 6 months. However I remain hopeful. These drugs are well tolerated but cytopenias can be a challenging issue. I tell patients that broadly speaking 4/10 would respond to therapy and mPFS remain in the range of about 6 months. These are not curative treatments.
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Mark FeslerApril 29, 2021Have seen responses in pre and post car T setting and in bmt/car ineligible. Roughly 20% of patients experience durable disease control neuropathy is main concern with polivy
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Mark FeslerApril 29, 2021Have seen responses in pre and post car T setting and in bmt/car ineligible. Roughly 20% of patients experience durable disease control neuropathy is main concern with polivy
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Mark FeslerApril 29, 2021Have seen responses in pre and post car T setting and in bmt/car ineligible. Roughly 20% of patients experience durable disease control neuropathy is main concern with polivy