TKI discontinuation proved to be safe and feasible in patients with CML with deep and durable molecular responses, introducing an additional treatment goal for these patients beyond overall survival. ...However, treatment interruption is a safe procedure only with appropriate patient selection and monitoring. Clinical and biological factors associated with better outcomes do not yet offer a precise stratification of patients according to their risk of relapse. This article aims at reviewing the leading studies present in the field in order to define eligibility criteria for discontinuation and predictors of success.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
In a first‐of‐its‐kind study, we assessed the capabilities of large language models (LLMs) in making complex decisions in haematopoietic stem cell transplantation. The evaluation was ...conducted not only for Generative Pre‐trained Transformer 4 (GPT‐4) but also conducted on other artificial intelligence models: PaLm 2 and Llama‐2. Using detailed haematological histories that include both clinical, molecular and donor data, we conducted a triple‐blind survey to compare LLMs to haematology residents. We found that residents significantly outperformed LLMs (p = 0.02), particularly in transplant eligibility assessment (p = 0.01). Our triple‐blind methodology aimed to mitigate potential biases in evaluating LLMs and revealed both their promise and limitations in deciphering complex haematological clinical scenarios.
In the evolving landscape of growing interest in large language models (LLMs) within medical research, an evaluation of the performance of current LLMs in the setting of haematopoietic stem cell transplantation was lacking. In this study, we proposed clinical haematological stories rich in clinical and molecular details to transplant specialists, LLMs, and haematology residents utilizing a triple‐blind methodology. The performance of LLMs was compared to that of haematology residents, considering as baseline values the consensus answer (CoA) of transplant specialists, defined as the predominant response from experts in each topic of the clinical case (transplantation eligibility, donor choice, conditioning regimen choice and transplant‐related mortality TRM).
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ALK-directed therapy is effective in
ALK
-positive lymphomas, but the appropriate duration of therapy is unclear. In two patients in whom crizotinib was discontinued, recurrence was rapid (within ...days). Further ALK-directed therapy induced responses.
To the Editor:
Crizotinib has been shown to have therapeutic activity in relapsed and resistant
ALK
-positive lymphomas.
1
–
3
Some patients receive treatment for more than 4 years without recurrence.
We describe two cases of abrupt relapse in patients with
ALK
-positive anaplastic large-cell lymphoma after discontinuation of crizotinib. Patient 1, a 26-year-old woman, began to receive therapy in June 2010. Complete remission was soon achieved, including negative results on quantitative polymerase-chain-reaction (PCR) testing to detect the nucleophosmin (NPM)-ALK messenger RNA in peripheral blood.
4
In February 2014, crizotinib was discontinued at the patient’s request, with the plan to reassess NPM-ALK . . .
Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as ...monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval CI = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profile.
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK‐positive or ROS1‐positive advanced non‐small‐cell lung cancer (NSCLC). ...However, ALK rearrangements are also implicated in other malignancies, including anaplastic large‐cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single‐arm, open‐label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK‐positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily. Primary endpoints were safety and objective responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or National Cancer Institute International Response Criteria. Forty‐four patients were enrolled (lymphoma, n = 18; IMT, n = 9; other tumors, n = 17). The objective response rate was 53% (95% confidence interval CI, 28–77) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30–93) for IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2–36) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively. The median duration of treatment was almost 3 years for patients with lymphoma and IMTs, with 2‐year progression‐free survival of 63% and 67%, respectively. The most common treatment‐related adverse events were diarrhea (45.5%) and vision disorders (45.5%), mostly grade 1. These findings indicate strong and durable activity of crizotinib in ALK‐positive lymphomas and IMTs. The safety profile was consistent with the known safety profile of crizotinib even with long‐term treatment.
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Crizotinib in Anaplastic Large-Cell Lymphoma Gambacorti-Passerini, Carlo; Pogliani, Enrico M; Messa, Cristina
New England journal of medicine/The New England journal of medicine,
02/2011, Volume:
364, Issue:
8
Journal Article
Peer reviewed
Open access
The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been shown to induce a response in lung cancers in which ALK is mutated. Crizotinib is also effective in anaplastic large-cell lymphoma, ...the tumor in which ALK rearrangement was initially detected.
To the Editor:
Crizotinib, an inhibitor of the anaplastic lymphoma kinase (ALK) tyrosine kinase, is active in non–small-cell lung cancers that have ALK expression.
1
ALK
is fused to several partner genes (mainly the gene encoding nucleophosmin) in the majority of anaplastic large-cell lymphomas (ALCLs). ALK tyrosine kinase activity represents the driver alteration in this disease.
2
ALK-positive ALCLs are highly responsive to cytotoxic drugs. However, relapses occur and require salvage therapy. We treated two patients who had relapsed ALK-positive ALCL with crizotinib at a dose of 250 mg twice daily. No glucocorticoids or other drugs with antineoplastic activity were allowed.
Patient . . .
Prognosis of Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, ...in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph+ ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. Seventy-one patients with a median age of 69 years were enrolled; 77% had a high comorbidity score. Complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. Only 7 patients underwent allogeneic hematopoietic stem cell transplantation. At 5 years, overall survival was 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24 were tested for mutation by Sanger sequencing, and 75% were T315I-positive. BCR-ABL1T315I was tested by allele-specific oligonucleotide reverse transcription–quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph+ ALL. Monitoring of BCR-ABL1T315I from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy.
•Dasatinib, combined with low-intensity chemotherapy, gave 36% 5-year overall survival in Ph+ ALL patients older than age 55 years.•Prospective monitoring of mutations may be useful to personalize therapy in Ph+ ALL patients not eligible for intensive therapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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