| 1. |
- Abalo, Kossi, et al.
(författare)
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Secondary malignancies among mantle cell lymphoma patients
- 2023
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 195
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:With modern treatments, mantle cell lymphoma (MCL) patients more frequently experience long-lasting remission resulting in a growing population of long-term survivors. Follow-up care includes identification and management of treatment-related late-effects, such as secondary malignancies (SM). We conducted a populationbased study to describe the burden of SM in MCL patients.Methods:All patients with a primary diagnosis of MCL, aged >= 18 years and diagnosed between 2000 and 2017 in Sweden were included along with up to 10 individually matched population comparators. Follow-up was from twelve months after diagnosis/matching until death, emigration, or December 2019, whichever occurred first. Rates of SM among patients and comparators were estimated using the Anderson-Gill method (accounting for repeated events) and presented as hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age at diagnosis, calendar year, sex, and the number of previous events.Results:Overall, 1 452 patients and 13 992 comparators were followed for 6.6 years on average. Among patients, 230 (16%) developed at least one SM, and 264 SM were observed. Relative to comparators, patients had a higher rate of SM, HRadj= 1.6 (95%CI:1.4-1.8), and higher rates were observed across all primary treatment groups: the Nordic-MCL2 protocol, R-CHOP, R-bendamustine, ibrutinib, lenalidomide, and R-CHOP/Cytarabine. Compared to Nordic-MCL2, treatment with R-bendamustine was independently associated with an increased risk of SM, HRadj= 2.0 (95%CI:1.3-3.2). Risk groups among patients were those with a higher age at diagnosis (p < 0.001), males (p = 0.006), and having a family history of lymphoma (p = 0.009). Patients had preferably higher risk of melanoma, other neoplasms of the skin and other hematopoietic and lymphoid malignancies.Conclusions:MCL survivors have an increased risk of SM, particularly if treated with R-bendamustine. The intensive treatments needed for long-term remissions are a concern, and transition to treatment protocols with sustained efficacy but with a lower risk of SM is needed.
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| 2. |
- Abrahamsson, Anna, et al.
(författare)
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Real world data on primary treatment for mantle cell lymphoma: a Nordic Lymphoma Group observational study.
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:8, s. 1288-1295
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Tidskriftsartikel (refereegranskat)abstract
- There is consensus that young patients with mantle cell lymphoma (MCL) should receive intensive immunochemotherapy regimens, but optimal treatment of elderly patients as well for as patients with limited or indolent disease is not defined. Our aim was to evaluate and compare outcome in relation to prognostic factors and first-line treatment in patients with MCL in a population-based data set. Data were collected from the Swedish and Danish Lymphoma Registries from the period of 2000-2011. A total of 1389 patients were diagnosed with MCL. During this period, age-standardized incidence MCL increased, most prominently among males. Furthermore, male gender was associated with inferior overall survival (OS) in multivariate analysis (HR 1.36; p=0.002). Forty-three (3.6%) patients with stage I-II disease received radiotherapy with curative intent, showing a 3 year OS of 93%. Twenty-nine (2.4%) patients followed a watch-and-wait approach and showed a 3 year OS of 79.8%. Among patients receiving systemic treatment, rituximab (n=766; HR 0.66; p=0.001) and autologous stem cell transplant (ASCT) (n=273; HR 0.55; p=0.004) were independently associated with improved overall survival in multivariate analysis. Hence, by a population-based approach, we were able to provide novel data on prognostic factors and primary treatment of MCL, applicable to routine clinical practice.
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| 3. |
- Albertsson-Lindblad, Alexandra, et al.
(författare)
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Ibrutinib inhibits antibody dependent cellular cytotoxicity induced by rituximab or obinutuzumab in MCL cell lines, not overcome by addition of lenalidomide
- 2019
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Ingår i: Experimental Hematology and Oncology. - : Springer Science and Business Media LLC. - 2162-3619. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Bruton's Tyrosine Kinase (BTK)-inhibitor ibrutinib is highly active in mantle cell lymphoma (MCL) but may inhibit response to anti-CD20 antibody as previously shown in CLL models. We investigated how antibody-dependent cellular cytotoxicity (ADCC) induced by type I/II anti-CD20 antibodies was affected by treatment with ibrutinib in MCL. Furthermore, we investigated if lenalidomide, a potential sensitizer to anti-CD20 treatment, could prevent an inhibitory effect of ibrutinib. Methods: Anti-CD20 (rituximab/obinutuzumab) opsonized MCL cell lines were co-cultured with ibrutinib (± lenalidomide) - exposed effector cells, and analyzed for evaluation of cell death. Results: Cell death induced by rituximab was reduced with 75% at 0.5 μM ibrutinib and with 52% at 0.1 μM ibrutinib when induced by obinutuzumab, even by addition of lenalidomide. Moreover, obinutuzumab was associated with higher rate of cell death compared to rituximab. Conclusion: Ibrutinib negatively affects anti-CD20 induced cell death in MCL, not reversed by lenalidomide. Explorations of sequential administration and selective BTK-inhibitors may reveal the optimal combination of novel agents in MCL.
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| 4. |
- Albertsson-Lindblad, Alexandra, et al.
(författare)
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Is there a role for immunomodulatory drugs in the treatment of mantle cell lymphoma?
- 2019
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Ingår i: Annals of Lymphoma. - 2616-2695. ; 3:2, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Although survival has improved in patients with mantle cell lymphoma (MCL) during the last two decades, thanks to intensified approach upfront and with anti-CD20 targeted treatment, the disease is still regarded as incurable and for the elderly/unfit patient population, there is need for more tolerable and effective treatment options. Immunomodulatory drugs (IMiDs) have demonstrated activity in MCL and could be regarded as attractive components of combinatory regimens for MCL, in light of their broad spectrum of activity and the potency to synergize with monoclonal antibody treatment. This review focus on the role of lenalidomide (L) as single agent in R/R MCL and in combinatory regimens. To date, one can conclude that L is an active agent in MCL, preferably when combined with anti-CD20 antibody, and may have a role as upfront treatment of elderly/unfit patients. Moreover, regimens including lenalidomide in combination with immunochemotherapy and in chemo-free regimens have shown activity, albeit associated with an increased risk of dose-limiting toxicity in untreated patient populations. Randomized trials evaluating the addition of L upfront, and phase I/II trials on L combined with other novel agents such as BTK- and bcl-2 inhibitors are underway and will further bring insight into the role of IMiDs in MCL.
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| 5. |
- Albertsson-Lindblad, Alexandra, et al.
(författare)
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Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:14, s. 1814-1820
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Tidskriftsartikel (refereegranskat)abstract
- For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter, open-label phase 1/2 trial, we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment for elderly patients with MCL. Patients >65 years with untreated MCL, stages II-IV were eligible for inclusion. Primary end points were maximally tolerable dose (MTD) of LEN and progression-free survival (PFS). Patients received 6 cycles every four weeks of L-B-R (L D1-14, B 90 mg/m(2) IV, days 1-2 and R 375 mg/m(2) IV, day 1) followed by single LEN (days 1-21, every four weeks, cycles 7-13). Fifty-one patients (median age 71 years) were enrolled from 2009 to 2013. In phase 1, the MTD of LEN was defined as 10 mg in cycles 2 through 6, and omitted in cycle 1. After 6 cycles, the complete remission rate (CRR) was 64%, and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3-year overall survival was 73%. Infection was the most common nonhematologic grade 3 to 5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in 3 patients: 2 Pneumocystis carinii pneumonia and 1 cytomegalovirus retinitis. Second primary malignancies (SPM) were observed in 8 patients (16%). LEN could safely be combined with R-B when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs, which may limit its use. This trial is registered at www.Clinicaltrials.gov as #NCT00963534.
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| 6. |
- Albertsson-Lindblad, Alexandra, et al.
(författare)
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Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years, the Nordic Lymphoma Group phase I+II trial NLG-MCL4
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 128:14, s. 1814-1820
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Tidskriftsartikel (refereegranskat)abstract
- For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untreated MCL, stage II-IV were eligible for inclusion. Primary endpoints were maximally tolerable dose (MTD) of LEN, and progression-free survival (PFS). Patients received six cycles q4w of L-B-R (L D1-14, B 90 mg/m(2) iv D1-2 and R 375 mg/m(2) iv D1) followed by single LEN (D1-21, q4w, cycles 7-13). 51 patients (median age 71 years) were enrolled 2009-2013. In phase I, the MTD of LEN was defined as 10 mg in cycles 2-6, and omitted in cycle 1. After six cycles, the complete remission rate (CRR) was 64% and 36% were MRD negative. At a median follow-up time of 31 months, median PFS was 42 months and 3 year overall survival was 73%. Infection was the most common non-hematological grade 3-5 event and occurred in 21 (42%) patients. Opportunistic infections occurred in three patients; 2 PCP and 1 CMV retinitis. Second primary malignancies (SPM) were observed in eight patients (16%). LEN could safely be combined with R-B, when added from the second cycle in patients with MCL, and was associated with a high rate of CR and molecular remission. However, we observed a high degree of severe infections and an unexpected high number of SPMs which may limit its use. http://clinicaltrials.gov: NCT00963534.
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| 7. |
- Albertsson Lindblad, Alexandra
(författare)
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Mantle cell lymphoma strategies in primary treatment
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mantle cell lymphoma (MCL) is associated with poor prognosis due to an aggressive clinical course. Being a rare disease, there are few randomized trials in MCL and there is no defined golden standard in primary treatment. This works aimed to (I) investigate outcome in relation to primary treatment in MCL based on population-based registry data, (II) to evaluate tolerability and efficacy of lenalidomide-rituximab-bendamustine (LBR) in newly diagnosed MCL patients within a phase I/II trial (MCL4) including (III) outcome in relation to genetic alterations, and (IV) to study how novel agents interfere with response to anti-CD20 antibodies. Our results showed that survival in MCL patients improved during 2000-2011, which partly could be explained by the introduction of rituximab and intensified treatment with high dose chemotherapy consolidation. We also found that treatment with radiotherapy to limited-stage disease and observation in non-symptomatic MCL were associated with long-term survival. In paper II and III, LBR was found to be an active combination in untreated MCL patients, except for cases harboring TP53 mutations, but associated with significant toxicity including second primary malignancies. In paper IV, we showed that the BTK-inhibitor ibrutinib, negatively affected the immune mediated cell death induced by a type I or II anti-CD20 antibody in MCL cell lines, not restored by addition of lenalidomide, a potential sensitizer to anti-CD20 ab. This work has provided data on important factors for outcome in MCL that may be taken into clinical use, such as active observation in non-symptomatic patients and rituximab and intensified approaches in primary treatment. Moreover, the addition of lenalidomide to BR could not be recommended as first-line treatment in MCL due to excessive toxicity and novel combinations with activity in elderly patients as well as in TP53 mutated MCL are highly warranted. Future studies, including in vitro models on drug interaction will clarify how novel agents should be combined for optimal use in MCL.
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| 8. |
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| 9. |
- Ekberg, Sara, et al.
(författare)
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Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation
- 2023
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Ingår i: Blood Advances. - : Elsevier. - 2473-9529 .- 2473-9537. ; 7:5, s. 866-874
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Tidskriftsartikel (refereegranskat)abstract
- Studies on late effects in patients with mantle cell lymphoma (MCL) are becoming increasingly important as survival is improving, and novel targeted drugs are being introduced. However, knowledge about late effects is limited. The aim of this population-based study was to describe the magnitude and panorama of late effects among patients treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT). The study cohort included all patients with MCL, recorded in the Swedish Lymphoma Register, aged 18 to 69 years, diagnosed between 2000 and 2014 (N = 620; treated with HD-ASCT, n = 247) and 1:10 matched healthy comparators. Patients and comparators were followed up via the National Patient Register and Cause of Death Register, from 12 months after diagnosis or matching to December 2017. Incidence rate ratios of the numbers of outpatient visits, hospitalizations, and bed days were estimated using negative binomial regression models. In relation to the matched comparators, the rate of specialist and hospital visits was significantly higher among patients with MCL. Patients with MCL had especially high relative risks of infectious, respiratory, and blood disorders. Within this observation period, no difference in the rate of these complications, including secondary neoplasms, was observed between patients treated with and without HD-ASCT. Most of the patients died from their lymphoma and not from another cause or treatment complication. Taken together, our results imply that most of the posttreatment health care needs are related to the lymphoma disease itself, thus, indicating the need for more efficient treatment options.
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| 10. |
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