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

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

Summary 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