Estimating the Lifetime Treatment Burden of Patients With Follicular Lymphoma: A Retrospective Study Using Real-World Multicenter Data

PURPOSE Although follicular lymphoma is characterized by long natural history and frequent relapses, data on the number of patients receiving subsequent therapy lines are scarce. To perform reliable health economical calculations for various treatment options, data regarding the lifetime number of therapy courses are needed. The purpose of this study was to use real-world data to create a model that could estimate the treatment burden over a 20-year period. MATERIALS AND METHODS We performed a 20-year simulation on the basis of retrospectively obtained multicenter data of 743 patients with follicular lymphoma. The simulation was carried out in two steps: First, a competing risk model on the basis of Weibull distribution was used to simulate the state transitions from diagnosis onward and from first-line therapy onward. Then, the data were completed by imputing on the basis of the existing data. Completion of data was repeated for 1,000 times to estimate reliability. RESULTS In 20 years, 97% (2.5-97.5 percentile range: 96%-98%), 66% (61%-70%), 34% (30%-41%), and 15% (9%-18%) of the patients received first-line, second-line, third-line, and fourth-line therapies, respectively. The median number of therapy lines received by each patient was two. CONCLUSION Despite long remissions, approximately two thirds of the patients receive at least two lines and one-third at least three lines of therapy during their lifetime

Female patients with follicular lymphoma have a better prognosis if primary remission lasts over 24 months

Findings regarding the role of sex in follicular lymphoma (FL) are contradictory and the prognostic value of sex among patients with early progression of disease (POD) remains unclear. We collected real-life data from nine hospitals in Finland and Spain including 1020 FL patients to study the influence of sex on disease outcome. The median follow-up duration was 67 months (range 0-226 months). Female patients showed better progression-free survival (PFS) (hazard ratio [HR], 0.720; 95% confidence interval [CI], 0.588-0.881), disease-specific survival (DSS) (HR, 0.653; 95% CI, 0.448-0.951), and overall survival (OS) (HR, 0.653; 95% CI, 0.501-0.853) than male patients. However, there were no significant sex differences in prognosis in patients with early POD. This study strengthens the understanding that male sex is an adverse prognostic factor for FL. However, this difference does not apply to patients with early POD.Peer reviewe

R-Bendamustine in the treatment of nodular lymphocyte-predominant Hodgkin lymphoma

Peer reviewe

Survival of patients with mantle cell lymphoma in the rituximab era : Retrospective binational analysis between 2000 and 2020

Mantle cell lymphoma (MCL) is a rare peripheral B-cell lymphoma characterised by eventual relapse and progression towards a more aggressive disease biology. With the introduction of rituximab- and cytarabine-based immunochemotherapy regimens, the prognosis of the disease has changed dramatically over the last two decades. To assess the real-world survival of patients with MCL, we used a population-based cohort of 564 patients with MCL who were diagnosed and treated between 2000 and 2020. Patient data were collected from seven Finnish treatment centres and one Spanish treatment centre. For the entire patient population, we report a 2-year overall survival (OS) rate of 77%, a 5-year OS of 58%, and a 10-year OS of 32%. The estimated median OS was 80 months after diagnosis. MCL is associated with increased mortality across the entire patient population. Additionally, we assessed the survival of patients after MCL relapse with the aim of establishing a cut-off point of prognostic significance. Based on our statistical analysis of survival after the first relapse, disease progression within 24 months of the initial diagnosis should be considered as a strong indicator of poor prognosis.publishedVersionPeer reviewe

Real-world Data : MCL2 Protocol Demonstrates Excellent Treatment Results among Patients with Mantle Cell Lymphoma Not Fulfilling the Original Trial Inclusion Criteria

Non peer reviewe

Clinical studies in adult lymphomas with special emphasis on late effects of treatments

Abstract Lymphomas are a heterogeneous group of malignancies of the lymphoid cells with almost a hundred different subtypes. In recent decades, there has been a major improvement in treatment results, and nowadays, only one-third of patients die due to lymphoma. As treatment results have improved, more attention has been paid to the adverse effects of treatment, which may be serious or even lead to death. The aim of this study was to describe treatment methods with a smaller risk of late adverse effects without impairing the treatment results. Follicular lymphoma (FL) is the second most common type of lymphoma in adults. Its prognosis is good, but relapses are common, and treatment must often be repeated, which causes a carcinogenic burden to the patient. Secondary malignancies are a significant late-onset adverse effect of lymphoma treatments. Currently, there are several treatment options available for FL. However, the risks of secondary malignancies associated with different treatment methods are not totally clear. In the present study, a higher risk for secondary haematological malignancies was observed after multiple lines of treatment. For secondary solid tumours, on the other hand, the greater risk was associated with the use of bendamustine. Diffuse large B-cell lymphoma is the most common lymphoma subtype. Patients are elderly and therefore more vulnerable to treatment-related adverse effects. Moreover, cardiac comorbidities are common in elderly patients, which may limit the use of certain treatment options. In this study, treatment results with standard therapy R-CHOP were retrospectively compared to those obtained with R-CEOP and R-CIOP, which are known to be less cardiotoxic. Treatment with R-CEOP was comparable to standard therapy, whereas results with R-CIOP were inferior. Nodular lymphocyte predominant Hodgkin lymphoma is a rare lymphoma subtype. These patients are traditionally treated with the same methods as those with classical Hodgkin lymphoma, although the diseases are very different biologically. Treatments used in Hodgkin’s disease are remarkably toxic. We examined the use of an R-bendamustine regimen among this group of patients. The results of the present study indicate that the late adverse effects of lymphoma treatments should be considered when selecting the most optimal treatment for lymphoma patients.Tiivistelmä Lymfoomat ovat heterogeeninen joukko imukudoksen syöpiä ja lähes sata erilaista alatyyppiä on tunnistettu. Lymfoomien hoitotuloksissa on tapahtunut merkittävää edistystä viime vuosikymmenien aikana ja tällä hetkellä vain noin kolmannes potilaista menehtyy tautiin. Hoitotulosten parantuessa on alettu kiinnittää enemmän huomiota myös hoitojen aiheuttamiin haittoihin, jotka saattavat olla huomattavan hankalia ja johtaa jopa potilaan menehtymiseen. Tutkimuksen tarkoituksena oli kuvata hoitomuotoja, joilla hoidon haittojen riski olisi pienempi ilman, että lymfooman hoitotulokset heikkenevät. Follikulaarinen lymfooma on aikuisten toiseksi yleisin lymfoomatyyppi. Taudin ennuste on hyvä, mutta uusiutuminen on yleistä ja tällöin hoitoja joudutaan toistamaan, mikä aiheuttaa potilaille merkittävän karsinogeenisen altistuksen. Mahdollisia hoitomuotoja on useita eikä eri hoitomuotojen aiheuttamaa sekundaarisen syövän riskiä vielä tarkasti tunneta. Tässä tutkimuksessa selvisi, että sekundaaristen hematologisten syöpien riski kasvoi hoitolinjojen lukumäärän kasvaessa. Bendamustiinin käyttö oli yhteydessä suurempaan kiinteiden kasvainten riskiin. Diffuusi suurisoluinen B-solulymfooma on yleisin lymfooman alatyyppi. Potilaat ovat iäkkäitä, mikä lisää riskiä saada hoitojen haittavaikutuksia. Lisäksi iäkkäillä potilailla sydänsairaudet ovat yleisempiä, mikä voi rajoittaa sydäntoksisten hoitovaihtoehtojen käyttöä. Tässä tutkimuksessa verrattiin sydänturvallisempien R-CEOP ja R-CIOP sytostaattiyhdistelmien tehoa R-CHOP standardihoitoon. R-CEOP.lla saadut hoitotulokset olivat verrattavissa standardihoitoon, mutta R-CIOP.lla saadut hoitotulokset olivat heikompia. Nodulaarinen lymfosyyttivaltainen Hodgkinin lymfooma on harvinainen Hodgkinin lymfooma. Näitä potilaita on perinteisesti hoidettu samoilla hoitomuodoilla kun muita Hodgkinin lymfoomia, vaikka taudit ovat biologialtaan hyvin erilaisia. Hodgkinin lymfooman hoidossa käytettävät hoidot ovat huomattavan toksisia. Tutkimuksessamme selvitimme R-Bendamustiinin käyttökelpoisuutta tällä potilasryhmällä. Tutkimustulokseemme osoittivat, että lymfoomahoitojen aiheuttamat haitat tulee huomioida hoitovalinnoissa ja hoitojen haittavaikutuksia tulee aktiivisesti pyrkiä vähentämään. Eri hoitomuotojen aiheuttamista myöhäishaittavaikutuksista on tärkeää olla tietoinen jo hoitopäätöksiä tehtäessä

Treatment of diffuse large B‐cell lymphoma in elderly patients:replacing doxorubicin with either epirubicin or etoposide (VP‐16)

Abstract Diffuse large B‐cell lymphoma (DLBCL) is the most common type of lymphoma. The standard therapy for DLBCL is R‐CHOP. The current 5‐year overall survival is 60% to 70% using standard frontline therapy. However, the use of doxorubicin and its cardiotoxicity is a major clinical problem and preexisting cardiac disease may prevent the use of doxorubicin. Age greater than 65 years is a significant risk factor for anthracycline‐induced cardiotoxicity, and therefore, the use of R‐CHOP is often withheld from elderly patients. The feasibility of replacing doxorubicin with either epirubicin or etoposide in patients who have risk factors for heart complications is analyzed here. Clinical data of 223 DLBCL patients were retrospectively collected from hospital records. Fifty‐five patients were treated with R‐CHOP, 105 with R‐CIOP (epirubicin instead of doxorubicin), 17 with R‐CEOP (etoposide instead of doxorubicin), and 31 with R‐CHOEP. Matched‐pair analysis was carried out between 30 patients treated with R‐CEOP and R‐CHOP. For all patients, the 2‐year progression‐free survival (PFS) was 73.6%. In patients treated with R‐CHOP, the 2‐year PFS was 84.2%, with R‐CIOP 64.4%, with R‐CEOP 87.7%, and with R‐CHOEP 83.2%. In matched‐pair analysis, the 2‐year PFS was 92.3% with R‐CHOP and 86.2% with R‐CEOP. The 2‐year disease specific survival was 100% with R‐CHOP and 86.2% with R‐CEOP. In conclusion, R‐CEOP offers reasonable PFS and disease specific survival in the treatment of DLBCL and good disease control can be achieved in elderly patients. Elderly patients with impaired cardiac function could benefit from the use of R‐CEOP instead of R‐CHOP. The results with R‐CIOP were unsatisfactory, and we do not recommend using this protocol in elderly patients with cardiac disease

Drug‐induced pneumonitis risk in diffuse large B‐cell/follicular lymphoma patients treated with R‐CHOP‐like regimen is associated with the use of granulocyte colony‐stimulating growth factors

Abstract Background Rituximab‐based combinations are the standard of care in diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma (FL). Despite being on market for over 20 years, some of the adverse effects associated with the use of rituximab are not well known. Drug‐induced interstitial pneumonitis (DIP) is a potentially fatal complication of the treatment. Granulocyte colony‐stimulating factors (G‐CSF) are supportive agents commonly used to prevent neutropenic infections. G‐CSF are reported to have pulmonary toxicity, but the risk of DIP is greater when used in combination with other potentially pulmotoxic agents. Methods In this retrospective study, we reported the G‐CSF use and risk of DIP in 234 DLBCL patients and 87 FL patients receiving R‐CHOP‐type immunochemotherapy. Results In 72% of patients, the treatment included a G‐CSF support. The overall incidence of treatment‐induced pneumonitis was 6.9% in this patient group. All the DIP cases (n = 16) were among patients receiving G‐CSF support (p = 0.03). Older age (over 60 years) and higher disease stage (Ann Arbor 3–4) also increased the risk of DIP. Conclusions These findings suggest that the use of G‐CSF increases the risk of DIP, when used in combination with rituximab‐containing regimen

Link between disease status at 24 months and mortality in follicular lymphoma

acceptedVersionNon peer reviewe

Refractoriness to rituximab-based therapy and elevated serum B2-microglobulin predict for inferior survival in marginal zone lymphoma

Short responses to immunochemotherapy predict for an inferior OS in follicular lymphoma. We set out to determine whether this is also the case in marginal zone lymphoma. A group of 139 marginal zone lymphoma (MZL) patients treated with front-line immuno- or immunochemotherapy (I/ICT) were categorized into I/ICT-refractory (non-response or relapse/progression within six months of treatment response assessment) or I/ICT-sensitive. Twenty-three patients (17%) were refractory. Refractory patients had inferior OS (4-yr probabilities of 57% vs. 83%, p = .0003) as did those with beta2-microglobulin (B2M)>3 mg/L (4-yr probabilities of 80% vs. 100%, p = .0029). On multivariable analysis they both showed a borderline significant correlation with OS (p = .06 and .07, respectively). B2M > 3 mg/L was also an adverse prognostic factor for progression-free survival in both univariable (4-yr probability of 61% vs. 83%, p = .02) and multivariable analysis (HR 2.9, p = .02). In conclusion, B2M and refractoriness to I/ICT may identify patients with MZL at higher risk of inferior survival