Chimeric antigen receptor (CAR) T-cell therapy is currently approved for the treatment of B-cell non-Hodgkin lymphomas and B-cell acute lymphoblastic leukemia. Prolonged hematological toxicity is an ...emergent concern following CAR T cells and occurred in 30% of patients with unknown mechanism. Few cases of myelodysplastic syndrome (MDS) following CAR T-cell therapy were reported and attributed to previous chemotherapies in heavily pretreated patients. The authors report the case of a patient with diffuse large B-cell lymphoma treated with axicabtagene ciloleucel who developed prolonged hematological toxicity by day 28. During the follow-up, the diagnosis of MDS was made. The patient underwent allogenic hematological stem cell transplantation. The patient remains in complete remission of his lymphoma and MDS 19 months after hematological stem cell transplantation.
Chimeric antigen receptor (CAR) T cell is a new type of immunotherapy that was recently validated for the treatment of some types of B-cell lymphoma and leukemia. One of the most recently reported side effects of CAR T cells is the appearance of anemia, thrombocytopenia and/or neutropenia lasting for a long duration. The authors report the case of a patient treated with CAR T cells for non-Hodgkin lymphoma who developed prolonged hematological toxicity. During follow-up, the diagnosis of myelodysplastic syndrome was made and the patient underwent allogenic bone marrow transplantation and remains in complete remission at last follow-up.
After failure of frontline therapy, patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) that does not respond to first-line salvage chemotherapy can be recommended second-line ...salvage chemotherapy. The available literature in this regard is weak, although many centers routinely offer this type of second-line salvage chemotherapy to their patients.
This retrospective study included transplant-eligible patients with RR-DLBCL treated at Gustave Roussy between January 2008 and April 2020. Eligible patients were those who received second-line salvage chemotherapy using R-DHAP or R-ICE in patients who experienced an insufficient partial response, stable disease, or progressive disease in response to first-line salvage chemoimmunotherapy using an alternative regimen.
Forty-six RR-DLBCL patients received second-line salvage regimen, which yielded an objective response rate of 33%, median progression-free survival of 2.1 months, and overall survival of 11.4 months. Twelve patients proceeded to autologous stem-cell transplantation (ASCT), of whom 70% remained alive 1 year after ASCT. To explore the impact of transplantation, a multivariate analysis (excluding response to the first-line salvage regimen because this covariate was totally embedded within the transplantation covariate), ASCT was associated with progression-free survival (hazard ratio = 0.16; 95% confidence interval, 0.06-0.42) and overall survival (hazard ratio = 0.27; 95% confidence interval, 0.08-0.88).
Second-line salvage chemotherapy with R-DHAP or R-ICE followed by ASCT leads to a favorable outcome in almost one third of patients with RR-DLBCL and offers a median overall survival of approximately 1 year. These data support the administration of second-line salvage chemotherapy followed by ASCT.
•Sixty percent of relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) fails to respond to first-line salvage chemoimmunotherapy.•A second-line salvage regimen followed by autologous stem-cell transplantation is an option in RR-DLBCL patients.•This study reports on outcomes of patients treated after second-line regimens, exploring whether one treatment sequence is more favorable than another.
This retrospective study of transplant-eligible patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) treated at Gustave Roussy between January 2008 and April 2020 found that second-line salvage chemotherapy with R-DHAP or R-ICE followed by autologous hematopoietic stem-cell transplantation leads to a favorable outcome in almost one third of patients with RR-DLBCL and offers a median overall survival of approximately 1 year.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell-free DNA sequencing. Here, we aimed to determine if the incidental detection ...of high-risk CH by liquid biopsy may reveal occult hematologic malignancies in patients with solid tumors.
Adult patients with advanced solid cancers enrolled in the Gustave Roussy Cancer Profiling study (ClinicalTrials.gov identifier: NCT04932525) underwent at least one liquid biopsy (FoundationOne Liquid CDx). Molecular reports were discussed within the Gustave Roussy Molecular Tumor Board (MTB). Potential CH alterations were observed, and patients referred to hematology consultation in the case of pathogenic mutations in
,
, or
, irrespective of the variant allele frequency (VAF), or in
,
,
,
,
,
, or
with VAF ≥ 10%, while also considering patient cancer-related prognosis.
mutations were discussed case-by-case.
Between March and October 2021, 1,416 patients were included. One hundred ten patients (7.7%) carried at least one high-risk CH mutation:
(n = 32),
(n = 28),
(n = 19),
(n = 18),
(n = 5),
(n = 4),
(n = 3),
(n = 3), and
(n = 2). The MTB advised for hematologic consultation in 45 patients. Overall, 9 patients of 18 actually addressed had confirmed hematologic malignancies that were occult in six patients: two patients had myelodysplastic syndrome, two essential thrombocythemia, one a marginal lymphoma, and one a Waldenström macroglobulinemia. The other three patients were already followed up in hematology.
The incidental findings of high-risk CH through liquid biopsy may trigger diagnostic hematologic tests and reveal an occult hematologic malignancy. Patients should have a multidisciplinary case-by-case evaluation.
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