We are analyzing https://link.springer.com/article/10.1007/s11899-023-00700-z.

Title:
Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) | Current Hematologic Malignancy Reports
Description:
Purpose of Review There have been significant advances in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) over the past two decades. However, the intention of treatment remains control of the disease and delay of progression rather than a cure which remains largely elusive. Considering that CLL is mostly seen in older patients, there are multiple factors that play a role in the selection of CLL beyond the frontline treatment. Here, we review the concept of relapsed CLL, factors that predispose to relapse, and therapeutic options available to this patient population. We also review investigational therapies and provide a framework for selection of therapies in this setting. Recent Findings Targeted therapies with continuous BTK inhibitors (BTKi) or fixed duration venetoclax plus anti-CD20 monoclonal antibody therapy have established superiority over chemoimmunotherapy in relapsed CLL and have become the preferred standard of care treatment. The second-generation more selective BTK inhibitors (acalabrutinib and zanubrutinib) have shown improved safety profile compared to ibrutinib. However, resistance to the covalent BTK inhibitors may emerge and is commonly associated with mutations in BTK or other downstream enzymes. The novel non-covalent BTK inhibitors such as pirtobrutinib (Loxo-305) and nemtabrutinib (ARQ 531) are showing promising activities for relapsed CLL refractory to prior covalent BTKi. Other novel therapies such as chimeric antigen receptor (CAR) T cell therapy have also shown significant activities for relapsed and refractory CLL. Measurable residual disease (MRD) assessment has a growing importance in venetoclax-based limited-duration therapy and there is mounting evidence that MRD negativity improves outcomes. However, it remains to be seen if this will become an established clinically significant endpoint. Further, the optimal sequence of various treatment options remains to be determined. Summary Patients with relapsed CLL now have more options for the treatment of the disease. The choice of therapy is best individualized especially in the absence of direct comparisons of targeted therapies, and the coming years will bring more data on the best sequence of use of the therapeutic agents.
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Keywords {🔍}

pubmed, article, google, scholar, cas, lymphocytic, chronic, leukemia, central, cll, patients, blood, relapsed, phase, study, ibrutinib, httpsdoiorgblood, treatment, oncol, btk, clin, venetoclax, therapy, relapsedrefractory, refractory, leukaemia, med, engl, httpsdoiorgs, httpsdoiorgjco, disease, therapies, cancer, eichhorst, treated, rituximab, resistance, lymphoma, httpsdoiorgnejmoa, inhibitor, targeted, inhibitors, chemoimmunotherapy, bcell, trial, obrien, hillmen, efficacy, lancet, survival,

Topics {✒️}

donor-derived cd19-redirected virus-specific antigen-independent cell-autonomous signalling causing graft-versus-host disease month download article/chapter chimeric antigen receptor-modified relapsed/refractory b-cell refractory b-cell malignancies b-cell malignancies relapsed org/professionals/physician_gls/pdf/cll small lymphocytic lymphoma venetoclax-based limited-duration therapy chronic lymphocytic leukaemia chimeric antigen receptor phosphatidylinositol 3-kinase p110delta chronic lymphocytic leukemia tyrosine kinase inhibitors car t-cell therapy related subjects accepted manuscript version b-cell malignancies kater ap previous venetoclax-based regimen stem-cell transplantation mantle cell lymphoma full article pdf chronic lymphoid leukemia superior progression-free survival article odetola showing promising activities byrd jc achieves antitumor activity btk inhibitor zanubrutinib btk inhibition targets animal subjects performed privacy choices/manage cookies selective bcl-2 inhibitor relapsed cll refractory relapsed/refractory cll oluwatobi odetola measurable residual disease prior targeted therapy selective btk inhibitors bcl2 confers resistance phase ii study shown significant activities durable molecular remissions additional information publisher covalent btk inhibitors covalent btk inhibitors drug-class resistance

Questions {❓}

Is BTKi or BCL2i preferable as first novel therapy in patients with CLL?
Is a BTKi or BCL2i preferable for first "novel" therapy in CLL?
Minimal residual disease assessment in CLL: ready for use in clinical routine?

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         description:There have been significant advances in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) over the past two decades. However, the intention of treatment remains control of the disease and delay of progression rather than a cure which remains largely elusive. Considering that CLL is mostly seen in older patients, there are multiple factors that play a role in the selection of CLL beyond the frontline treatment. Here, we review the concept of relapsed CLL, factors that predispose to relapse, and therapeutic options available to this patient population. We also review investigational therapies and provide a framework for selection of therapies in this setting. Targeted therapies with continuous BTK inhibitors (BTKi) or fixed duration venetoclax plus anti-CD20 monoclonal antibody therapy have established superiority over chemoimmunotherapy in relapsed CLL and have become the preferred standard of care treatment. The second-generation more selective BTK inhibitors (acalabrutinib and zanubrutinib) have shown improved safety profile compared to ibrutinib. However, resistance to the covalent BTK inhibitors may emerge and is commonly associated with mutations in BTK or other downstream enzymes. The novel non-covalent BTK inhibitors such as pirtobrutinib (Loxo-305) and nemtabrutinib (ARQ 531) are showing promising activities for relapsed CLL refractory to prior covalent BTKi. Other novel therapies such as chimeric antigen receptor (CAR) T cell therapy have also shown significant activities for relapsed and refractory CLL. Measurable residual disease (MRD) assessment has a growing importance in venetoclax-based limited-duration therapy and there is mounting evidence that MRD negativity improves outcomes. However, it remains to be seen if this will become an established clinically significant endpoint. Further, the optimal sequence of various treatment options remains to be determined. Patients with relapsed CLL now have more options for the treatment of the disease. The choice of therapy is best individualized especially in the absence of direct comparisons of targeted therapies, and the coming years will bring more data on the best sequence of use of the therapeutic agents.
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      description:There have been significant advances in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) over the past two decades. However, the intention of treatment remains control of the disease and delay of progression rather than a cure which remains largely elusive. Considering that CLL is mostly seen in older patients, there are multiple factors that play a role in the selection of CLL beyond the frontline treatment. Here, we review the concept of relapsed CLL, factors that predispose to relapse, and therapeutic options available to this patient population. We also review investigational therapies and provide a framework for selection of therapies in this setting. Targeted therapies with continuous BTK inhibitors (BTKi) or fixed duration venetoclax plus anti-CD20 monoclonal antibody therapy have established superiority over chemoimmunotherapy in relapsed CLL and have become the preferred standard of care treatment. The second-generation more selective BTK inhibitors (acalabrutinib and zanubrutinib) have shown improved safety profile compared to ibrutinib. However, resistance to the covalent BTK inhibitors may emerge and is commonly associated with mutations in BTK or other downstream enzymes. The novel non-covalent BTK inhibitors such as pirtobrutinib (Loxo-305) and nemtabrutinib (ARQ 531) are showing promising activities for relapsed CLL refractory to prior covalent BTKi. Other novel therapies such as chimeric antigen receptor (CAR) T cell therapy have also shown significant activities for relapsed and refractory CLL. Measurable residual disease (MRD) assessment has a growing importance in venetoclax-based limited-duration therapy and there is mounting evidence that MRD negativity improves outcomes. However, it remains to be seen if this will become an established clinically significant endpoint. Further, the optimal sequence of various treatment options remains to be determined. Patients with relapsed CLL now have more options for the treatment of the disease. The choice of therapy is best individualized especially in the absence of direct comparisons of targeted therapies, and the coming years will bring more data on the best sequence of use of the therapeutic agents.
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         Oncology
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