Progression-free survival after front line, second line and third line in patients with follicular lymphoma treated in clinical practice.

BACKGROUND: The modern-day therapeutic landscape for follicular lymphoma (FL) includes a number of highly effective therapies. PATIENTS AND METHODS: We set out to determine progression-free survival (PFS) after front line, second line, and third line of therapy on the basis of relevant biological characteristics and therapeutic choices. Patients (n = 743, 51% females, median 60 years old) diagnosed with grade 1-2 FL between 1997 and 2016 in nine institutions were included. RESULTS: The median PFS1, PFS2, and PFS3 were 8.1 years (95% confidence interval [CI]: 7-9.3 years), 4.2 years (95% CI: 2.8-5.6 years) and 2.2 years (95% CI 1.7-2.8 years). We found longer PFS1 for (1) females, (2) younger age, (3) lower-risk follicular lymphoma international prognostic index (FLIPI), (4) standard intensity (over low intensity) regimens and (5) immunochemotherapy strategies and (6) maintenance rituximab. We found a shorter PFS2 for patients who received front-line immunochemotherapy. Older age at diagnosis correlated with a shorter PFS3. Intensity of front-line chemotherapy, maintenance, or POD24 status did not correlate with PFS2 or PFS3 in this dataset. INTERPRETATION: With current immunochemotherapy strategies, the natural course of FL is characterized by shorter-lasting remissions after each relapse. It will be interesting to see whether new therapies can alter this pattern.

Front-line and second-line treatment for mantle cell lymphoma in clinical practice: A multicenter retrospective analysis.

BACKGROUND: There are few reports of clinical practice treatment patterns and efficacy in mantle cell lymphoma (MCL). MATERIALS AND METHODS: We retrospectively studied a large, multicenter, cohort of patients with MCL diagnosed between 2000 and 2020 in eight institutions. RESULTS: 536 patients were registered (73% male, median of 70 years). Front-line treatment was based on high-dose cytarabine, bendamustine, and anthracyclines in 42%, 12%, and 15%, respectively. The median PFS for all patients was 45 months; 68, 34, and 30 months for those who received high-dose cytarabine-based, bendamustine-based and anthracycline-based therapy. 204 patients received second-line. Bendamustine-based treatment was the most common second-line regimen (36% of patients). The median second-line PFS (sPFS) for the entire cohort was 14 months; 19, 24, and 31 for bendamustine-, platinum-, and high-dose cytarabine-based regimens, with broad confidence intervals for these latter estimates. Patients treated with cytarabine-based therapies in the front-line and those with front-line PFS longer than 24 months had a substantially superior sPFS. CONCLUSION: Front-line treatment in this cohort of MCL was as expected and with a median PFS of over 3.5 years. Second-line treatment strategies were heterogeneous and the median second-line PFS was little over 1 year.

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.

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.

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.

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.

Mortality among patients with low-grade follicular lymphoma: A binational retrospective analysis.

BACKGROUND: The life expectancy of patients with follicular lymphoma (FL) has improved considerably since the introduction of rituximab. This study examined the proportion of deaths from progressive lymphoma and the impact of FL on survival compared with that in the general population. METHODS: Altogether, 749 patients with grades 1 and 2 FL in 9 institutions between 1997 and 2016 were enrolled. Competing risk models were used to estimate the cumulative incidences of deaths from progressive lymphoma and from other reasons. Excess mortality was analyzed with respect to the corresponding background populations standardized for age and sex using the excess mortality model based on the penalized spline approach. RESULTS: The median follow-up duration was 69 months (range, 0-226 months). The estimated 10-year overall, disease-specific, and net survival rates were 72.4%, 86.6%, and 86.4%, respectively. The cumulative incidence of deaths from progressive lymphoma was slightly smaller than that of other causes in the study population (estimated 10-year cumulative incidences: 12.3% [95% CI, 9.6%-15.3%] and 15.4% [95% CI, 12.2%-18.8%], respectively). Excess mortality was observed for up to 10 years after diagnosis, and it slightly increased with time. CONCLUSIONS: Deaths from progressive lymphoma are nearly as common as deaths from other causes in FL patients during the rituximab era. Despite the improvements in survival, there was evidence of excess mortality resulting from FL for at least 10 years after diagnosis.

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.

Incidence of solid cancer in patients with follicular lymphoma.

Introduction: Patients with follicular lymphoma (FL) have classically had a higher risk of solid cancers than the general population, but there is little data available in patients diagnosed and treated with modern day regimens.Material and methods: We conducted a retrospective multicenter study assessing the cumulative incidence of solid cancers other than nonmelanoma skin cancer in patients with FL between 1997 and 2016 and determined the standardized incidence ratio (SIR) to compare the incidence of solid cancers with that of the general populationResults: Among 1002 FL patients with 7 years of median follow-up, we found 74 solid cancers (most common breast [n = 19], lung and colon [n = 9 each]). The cumulative incidence was 3.8% at 5 years (95%CI 2.6-5.2) from the time of diagnosis and 4.4% at 5 years (95%CI 3.1-5.9%) from the time of front-line treatment. Although a comparison of all front-line strategies did not reveal differences in the risk of solid cancers, patients treated with anthracycline-based regimens appeared to have a lower incidence than those treated with bendamustine-based strategies (2.8% vs. 6.9%). However, patients receiving the former regimen were younger than the latter. On multivariable analysis, older age was correlated with the incidence of solid cancer and bendamustine-based treatment was of borderline significance. SIR for any solid cancer was 1.22 (95%CI 0.91-1.64), indicating no increased risk of solid cancer in patients with FL over that of the general population. However, on subgroup analyses, female patients treated with bendamustine-based strategies appeared to have a greater risk (SIR 3.85 [95%CI 1.45-10.27])Discussion: The incidence of solid cancer in this cohort of patients with FL was low and not greater than in the general population. However, the risk may be greater in female patients treated with bendamustine.

Risk of secondary haematological malignancies in patients with follicular lymphoma: an analysis of 1028 patients treated in the rituximab era.

Follicular lymphoma (FL) is the most common indolent lymphoma. Currently there are many comparable treatment options available for FL. When selecting the most optimal therapy it is important to consider possible late effects of the treatment as well as survival. Secondary haematological malignancy (SHM) is a severe late effect of treatments, but the incidence of SHMs is still largely unknown. The goal of the present study was to determine the incidence of SHMs and how therapeutic decisions interfere with this risk. The study included 1028 FL patients with a median follow-up time of 5·6 years. The 5-year risk of SHM was 1·1% and the risk was associated with multiple lines of treatment (P = 0·016). The 5-year risk of SHM was 0·5% after the first-line treatment and 1·6% after the second-line. The standardized incidence ratio (SIR) was 6·2 (95% confidence interval 3·4-10·5) for SHM overall. This retrospective study found that the risk of SHM was low after first-line treatment in FL patients from the rituximab era. However, the risk of SHM increases with multiple lines of treatment. Therapeutic approaches should aim to achieve as long a remission as possible with first-line treatment, thereby postponing the added risk of SHM.

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.