There is no standard treatment for transformed lymphoma. Your medical team recommends the most appropriate treatment for you based on: your preferences. If you haven’t had it before, you are likely to be offered the standard chemotherapy for the type of high-grade lymphoma your lymphoma has transformed into.
When to treat follicular lymphoma?
There are ways to treat follicular lymphoma, but the condition often returns. Healthcare providers are hopeful newer treatments may mean a cure for follicle lymphoma is on the horizon. Cancer Answer Line 866.223.8100 Appointments & Locations Download a Treatment Guide Search Clinical Trials Symptoms and Causes Diagnosis and Tests
What is the survival rate for follicular lymphoma?
· Develop a treatment strategy for patients with transformed follicular lymphoma Describe the time to transformation for high-risk patients and the need for a biopsy for patients with early progressing...
What are the signs and symptoms of follicular lymphoma?
· The choice of treatment for a patient presenting with transformed lymphoma who has been previously treated is strongly influenced by the prior therapy. For patients who have …
How fast does follicular lymphoma grow?
Common combination regimens include: R-Bendamustine (rituximab and bendamustine) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) R-CVP …
How is transformed lymphoma treated?
If aggressive chemotherapy alone fails to induce remission, then second-line treatments that may be considered include radioimmunotherapy and high-dose chemotherapy followed by stem cell transplantation. There is no single treatment for all patients with transformed lymphoma.
Is transformed follicular lymphoma curable?
The median posttransformation survival of 5 years suggests improved outcomes for transformed FL in the modern era. Five-year progression-free and overall survival (66% and 88%) are favorable for patients with evidence of transformation at diagnosis.
How do you know if follicular lymphoma has transformed?
The most common signs and symptoms of transformed lymphoma include: swollen lymph nodes that are growing quickly. rapid swelling of your liver or your spleen (an organ of your immune system) weight loss, night sweats or fevers ('B symptoms')
What is the latest treatment for follicular lymphoma?
The newest drug to be approved by the FDA for follicular lymphoma is Copiktra (duvelisib), an oral drug that targets PI3K-alpha, a protein that is overexpressed in many B-cell cancers, including follicular lymphoma, and encourages the growth of cancerous cells.
Can transformed lymphoma be cured?
High Dose Chemotherapy Treatment for Transformed NHL. Patients with transformed lymphomas may achieve a significantly higher rate of long-term survival when treated with high-dose therapy and stem cell transplantation, according to an early study published in the Journal of Clinical Oncology.
Is Stage 3 follicular lymphoma curable?
For people with stage II, III, or IV disease (table 1), the average survival is greater than 20 years. Despite its slow-growing nature, it is unclear whether most cases of follicular lymphoma can be cured with currently available therapies.
Can follicular lymphoma become more aggressive?
There is a risk in individuals with follicular lymphoma that the cancer can go under a transformation from a slow-growing (indolent) form into a more aggressive form called diffuse large B-cell lymphoma (DLBCL). As many as 30-40% of individuals may experience aggressive transformation of indolent follicular lymphoma.
What chemo is used for follicular lymphoma?
Commonly used chemotherapy regimens for follicular lymphoma include rituximab (Rituxan; Genentech, Biogen) plus bendamustine or CHOP chemotherapy. In general, these combinations result in an overall response rate of 90%, with approximately 40% of patients achieving complete remission.
Can follicular lymphoma grow quickly?
Follicular lymphoma often grows slowly, although in some people it can develop more rapidly. Treatment is generally successful, but at some point, the lymphoma usually comes back (relapses) and needs more treatment to keep it under control. It is hard to predict how long it might be before you need more treatment.
Can you live 40 years with follicular lymphoma?
The median age at diagnosis is about 60 years and there is a slight female predominance. Despite recent improvements in survival, follicular lymphoma remains an incurable disease, with a median overall survival of ∼14 years.
Can you live a long life with follicular lymphoma?
Follicular lymphoma is slow-growing cancer. People diagnosed with the disease may not find a cure but can still live for a long time with it. The five-year survival rate for follicular lymphoma is 80-90% with patients surviving for a median of 10-12 years.
What is first line treatment for follicular lymphoma?
Answer: We consider bendamustine and rituximab (BR) as our preferred regimen as first-line therapy for a symptomatic patient with follicular lymphoma.
How often do FL transformations occur?
The reported frequency of higher-grade FL transformation varies significantly, ranging from 10% to 60% of patients (Table 1). The wide range of reported frequency of the higher-grade histological transformation most probably relates to the methodological differences in the reported studies. Such differences include the policy regarding re-biopsy of relapse or disease progression, variable inclusion of autopsy data in the different series, inclusion of cases in which transformation was defined by clinical characteristics and variable duration of FL patients’ follow-up and surveillance. Most previous clinical and pathological surveys assessing the frequency of FL transformation did not determine the clonality of the paired pre-and post-transformation lymphomas and thus did not distinguish between a true histological transformation (which represent evolution of the same clone) versus secondary de novoaggressive lymphomas, which are clonally unrelated to the antecedent FL and thus do not represent true transformation. Moreover, the reported frequency of FL transformation also depends on the size of the cohort used for analysis. No prospective studies with pre-defined uniform criteria for re-biopsy have been performed and all the reported studies are based on retrospective reviews. Therefore, in the absence of prospective long-term studies with an aggressive policy of re-biopsy for all suspected clinical transformations and/or new lesions, the true frequency of histological transformation of FL cannot be reliably estimated. Acker et alreported transformation risk of 20% at 5 years and 60% at 8 years of observation[7]. Ersboll et al[12]and Montoto et al[14], who defined transformation solely by histological criteria, reported 30% and 17% of transformation at 5 years and 56% and 28% probability of transformation at 10 years, respectively. Bastion et al[13]and Al-Tourah et al[15], who defined transformation by either histological or clinical criteria, reported 22% and 15% probability of transformation at 5 years and 31% and 30% probability of transformation at 10 years, respectively. Overall, these studies suggest a cumulative rate of transformation of 3% per year. While Bastion et al[13] and Montoto et al[14] suggested the presence of a plateau in the risk of transformation after 6 and 12 years of follow up, respectively, with no further increase in the rate of transformation during longer follow up, there was no evidence of a plateau in the risk of transformation in the studies by Horning et al[9] and Al-Tourah et al[15], indicating a continuous increase in the actuarial risk of FL transformation over time. This increase in the probability of transformation over time and its occurrence in both treated and un-treated FL patients suggest that the change to a more aggressive histology associated with a more aggressive clinical behavior may represent an inherent potential of FL.
What is the gold standard for lymphoma?
The current gold standard definition of higher-grade transformation to more aggressive lymphomas is based on a histological demonstration of an increase in the proportion of large cells infiltrating the lymph nodes diffusely and leading to effacement of the follicular architecture.
What is the loss of TNFRSF14gene?
Loss of TNFRSF14gene, a candidate tumor suppressor
What are the biological factors associated with histologic transformation of FL to DLBCL?
These include both genetic alterations harbored by the malignant B cells and factors that influence the tumoral microenvironment. UPD = uniparental dizomy, FDC = follicular dendritic cells, PD = programmed death and MVD = microvessel density.
What is the concomitant of the transformation?
Concomitant with the transformation is loss of the follicular architecture and an increase in the mitotic rate in large part due to the increased centroblasts. More common changes in the immunophenotype relate to changes in the non-neoplastic cells.
What is transformation of FL?
Transformation of FL represents a spectrum of histologies, many of which can be difficult to classify using a World Health Organization (WHO) schema largely established for de novoNHLs (see Table 2). The most common histology identified in follow-up biopsies of patients with FL is DLBCL (see Figure 1). These cases typically reveal classic centroblastic morphology, but may show vague remnants of the underlying FL. The second most common histology encountered is largely encapsulated with the new WHO gray zone category of unclassifiable B cell lymphoma with features intermediate between DLBCL and Burkitt lymphoma (BL)[22]. This category contains cases previously diagnosed as Burkitt-like lymphoma; terminology that is no longer recommended[56, 57]. These cases show a diffuse architecture with a mixture of medium-to large transformed cells and may reveal a starry-sky pattern and moderate numbers of mitotic figures[22, 58, 59]. A resemblance to BL is often found, particularly at low magnification. However, variation in nuclear size and shape typically precludes a straight-forward diagnosis of BL. These cases typically show uniform BCL2 protein expression and the BCLU category is enriched for dual-translocation/double-hit lymphomas harboring both BCL2and MYCtranslocations[22, 58]. Dim CD20 expression has also been recently described as a feature of double-hit lymphomas[60]. Half of the double-hit lymphomas in clinical practice can arise de novolacking a history of antecedent FL and present as aggressive neoplasms that are presumed to represent transformation of clinically silent FL[61-65]. Transformed FL should never be diagnosed as BL (exceptions would include a clonally unrelated BL as a second lymphoma), as the presence of the characteristic FL translocation, the t(14;18), and strong cytoplasmic expression of BCL2 would by definition preclude a diagnosis of classic BL. Moreover, cytogenetic analysis of transformed FL would typically reveal cytogenetic complexity, a feature not found in de novoBL[66, 67].
What is the immunophenotype of FL?
The immunophenotype of FL is similar to germinal center B cells. The neoplastic cells of FL typically express CD19, CD20, CD22, and CD79a and show surface Ig expression (sIG of IgM +/- IgD, IgG or rarely IgA). Most cases are positive for BCL2, BCL6 and CD10. Typically CD5 and CD43 are negative. CD10 and BCL6 are often down-regulated and show less intense staining in the inter-follicular regions. Both HGAL and LMO2 have recently been shown to be very useful markers in the diagnosis of FL, particularly in cases with variant immunoarchitectural patterns[34]. The proliferative rate of FL is typically low, but can be quite variable and may be associated with outcome[35, 36]. A subset of grade 3b FL cases may show less frequent expression of CD10, may express MUM1 and may lack t(14;18) and reveal BCL6translocations[37-39].
What is an Indolent lymphoma?
Indolent lymphomas, including FL, marginal zone lymphoma, lymphoplasmacytic lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma, have the potential to undergo histologic transformation (HT) into an aggressive disease with a mandatory change in treatment approach.
What is FL transforming to?
Patient with FL transforming to HGBL-DHL/THL, showing massive infiltration of the right chest wall and axillary adenopathy.
Can lenalidomide be used for TFL?
Despite the promise of the approaches outlined above, many patients are either ineligible for transplant or cellular therapy or experience relapse despite these modalities. Again, there are no trials specifically dedicated to tFL or other patients with transformed indolent lymphoma, and nearly all data are derived by culling subsets from trials designed for relapsed/refractory DLBCL. An interesting observation is that there may be a role for lenalidomide in tFL despite this being a germinal center–derived disease. In a small prospective trial, lenalidomide monotherapy had an overall response rate of 57% with a median duration of response of 12.8 months in relapsed and refractory tFL. 24 When combined with rituximab, a small prospective trial showed a response rate of ∼50%, but durability was limited. 25 The addition of lenalidomide to tafasitamab appears active in transformed indolent lymphomas, with all patients responding; however, there were only 7 patients with transformed lymphomas included in this trial. 26 Other regimens approved for DLBCL either had very limited patients with tFL or excluded them entirely. For example, the recently approved regimen of polatuzumab-BR excluded patients with transformed lymphomas. 27 The median survival of patients with tFL in the relapsed/refractory setting is abysmal, and focused and biologically rational studies are needed.
Is cellular therapy approved for TFL?
To date, there are 2 US Food and Drug Administration–approved options, with a third agent close to approval.
Is allo-HCT a relapse?
Allogeneic hematopoietic stem cell transplant (allo-HCT) is also an option for patients with relapsed/refractory tFL. Several factors limit its widespread use, including higher nonrelapse mortality and major questions regarding the optimal timing of allo-HCT. One of the few side-by-side analyses, albeit in a registry and not a prospective trial, found no difference in PFS or OS between those treated with allo-HCT and those who received auto-HCT, but a significantly higher nonrelapse mortality of 23% vs 5%, respectively, was reported. 19 It should be noted that there are fundamental differences in patients selected for auto-HCT and those selected for allo-HCT, so these types of comparisons are difficult to interpret. According to the Center for International Blood and Marrow Transplant Research ( https://www.cibmtr.org/ReferenceCenter ), the number of allo-HCTs performed for lymphomas has declined in recent years as the introduction of cellular therapy has further challenged its role.
Can tFL patients be treated with chemo?
There is sufficient evidence that patients with tFL previously treated with anthracycline-based chemoimmunotherapy for their underlying FL benefit from salvage chemotherapy and a consolidative autologous stem cell transplant if they have chemosensitive disease.
Does chemoimmunotherapy affect survival?
Prior anthracycline exposure appears to confer worse survival (21% vs 66%; P < .001) than in those without prior anthracycline exposure. 1 The National Comprehensive Cancer Network found that the 2-year OS was substantially worse (35% vs 100%; P = .03) for patients treated with chemotherapy (mainly anthracycline based) before HT. 16 A Spanish registry series reported that 5-year OS for patients treated with chemotherapy before HT was 55% (95% confidence interval, 38%-69%) vs 81% (95% confidence interval, 53%-93%; P = .009) for those who had not received prior chemotherapy. 17 The poor prognosis for patients with prior chemoimmunotherapy may be independent of prior anthracycline exposure; for example, patients with HT after prior bendamustine, rituximab (BR) have a 2-year OS of only 40%. 9 In this Canadian report, the authors reported that the main driver of POD24 was occult or early transformation.
How long does monoclonal antibody therapy last?
Some monoclonal antibodies can also be used as maintenance therapy for up to two years to prolong remission for patients with no signs of lymphoma. Another treatment sometimes used for FL is radioimmunotherapy (RIT) using an agent such as yttrium-90 ibritumomab tiuxetan (Zevalin), which is a radioactive particle connected to an antibody that targets cancer cells.
Can you use rituximab alone for FL?
In more advanced stages, physicians may use one or more chemotherapy drugs or the monoclonal antibody rituximab (Rituxan), alone or in combination with other agents.
What is the highest priority in lymphoma clinical trial research?
Identification of novel therapies for this vulnerable group has emerged as the highest priority in lymphoma clinical trial research by the National Cancer Institute. 30 Complicating matters is a lack of robust end points to know when we have achieved success for patients with early relapse. Additionally, the best approach for asymptomatic early-relapsing patients with low tumor burden has not been specifically evaluated. Response rates and duration of response are metrics being tested in clinical studies, but they have not been established as gold standards of meaningful outcome. However, the goal for any next therapy involves overcoming chemotherapy resistance, targeting mechanisms of disease, and achieving durable disease control. We consider clinical trial participation as the primary treatment option ( Figure 2) for patients experiencing POD24, given the limited prospective evidence guiding treatment decisions for this population.
How long does it take for a patient to relapse after chemo?
Those with relapse within 12 months after chemoimmunotherapy had a standard mortality ratio of 17.63 and 19.10 (replication cohort). However, patients remaining event free at 12 months had excellent outcomes, with survival approaching that of the general population.
Does obinutuzumab affect POD24?
Type of induction chemotherapy may influence survival of patients experiencing POD24. In the GALLIUM study using obinutuzumab-based induction for frontline FL treatment, an exploratory analysis evaluated the frequency and impact of POD24. Risk of mortality from POD24 was increased, with HR of 26 (95% CI, 16.2-40.3), and risk was proportional to how early progression occurred. Obinutuzumab-based chemotherapy was associated with a 34% reduction in the number of POD24 events. However, postprogression survival was similar in all treatment groups. 13 Other recent analyses of POD24 after bendamustine-based induction also suggested a decreased risk of POD24 events (9% to 12%), with similarly poor outcomes. 18, 19
How long does it take for a FL to relapse?
Early relapse has been defined broadly as FL recurrence within 2 years of chemoimmunotherapy or within 2 years of diagnosis. For the purposes of this review, we will define early relapse as progression of disease within 24 months of frontline FL chemoimmunotherapy initiation (POD24). This definition is based upon disease progression assessed clinically and/or radiographically. However, histologic confirmation of disease progression is recommended to aid in subsequent management. The initial selection of 24 months was selected as the time during which most early events occurred consistently and reproducibly across FL studies. 10-12 Moreover, the observation that ∼20% of patients experience disease progression by 24 months has been validated multiple times by independent investigators. 13-17
Does rituximab cause relapse?
Early relapse of follicular lymphoma after rituximab-based biologic doublet upfront therapy is associated with increased risk of death: a combined analysis from CALGB studies 50402, 50701 and 50803 (Alliance) [abstract]
Does idelalisib inhibit PI3K?
Phosphatidylinositol 3-kinase (PI3K) inhibition has also demonstrated significant activity in patients with relapsed FL. Developed to target the B cell–restricted δ isoform, idelalisib was approved for patients who have received 2 prior therapies based on a phase 2 trial in patients refractory to rituximab and alkylating agents. Of 125 indolent lymphoma patients, idelalisib demonstrated an ORR of 57% (56% specifically in FL), with 6% CR. 42 Median duration of response was 13 months, and median PFS was 11 months. Concomitant inhibition of PI3K α and γ isoforms with copanlisib and duvelisib has demonstrated similar results in this same double-refractory population. 43-45 A post hoc subgroup analysis of the idelalisib-treated patients was performed to evaluate outcomes with early progression after first-line chemoimmunotherapy. 46 Of the 37 patients identified, efficacy was similar to that in the larger group, including 57% objective response rate, 14% CR, and median PFS of 11 months. Umbralisib is a PI3Kδ inhibitor with a distinct chemical structure allowing for once-daily dosing. Phase 1 data suggest a similar pattern of response, with a potentially improved safety profile, compared with other PI3Kδ inhibitors. This may be related to increased specificity for the δ isoform and subsequently less perturbation of regulatory T cells. 47-49
What is GEP in lymphoma?
The Lymphoma Study Association analyzed data from the PRIMA study using gene expression profiling (GEP) before treatment to establish which gene signatures were enriched for treatment failure and poor PFS. 5 A 23-gene predictor characterized by the presence of B-cell centroblasts was implicated in greater disease aggressiveness and was capable of distinguishing patient outcome independently of the FLIPI, with validation in 3 international cohorts. This GEP discriminates patients at greater risk of POD24 (38%) compared with other prognostic models. In addition to these biomarkers, PET is under consideration for use alone and in combination with clinical and molecular markers (eg, circulating tumor DNA) to identify the highest-risk patients, but further validation is required. 23, 24
Transformed follicular lymphoma
Hi, my husband was diagnosed with non Hodgkins follicular lymphoma (low grade) stage 4 in 2005. He was on watch and wait for a while, then in 2007 had to have RCVP chemo. This was followed later by a course of Rituximab. Recently he has had terrible drenching night sweats, weight loss etc.
Transformed follicular lymphoma
I am sorry to hear that the follicular lymphoma has transformed into aggressive Hodgkin's Lymphoma and it's unlucky that this is a rare transformation. It's reassuring news though that it can potentially be cured by chemo.
What to do if you suspect transformation?
If transformation is suspected, the Doctor will arrange for a scan such as a CT or PET scan and arrange to take a biopsy to confirm if the cells are growing at a faster rate.
What is the treatment for stem cell transplant?
If your disease returns very quickly after your first treatment (commonly referred to as early relapse), your doctor may consider using a more intensive treatment (also known as ‘Salvage chemotherapy’).
Is FL treated in refractory or transformed?
There is currently no standard way in which relapsed, refractory or transformed FL is treated . Your doctor will take the following factors into account:
Can FL transform into B cell?
It’s possible that after diagnosis with FL, the disease can transform from an indolent low grade lymphoma into a faster-growing type of lymphoma like ‘Diffuse Large B Cell’ Lymphoma. This will need to be treated more aggressively like a high grade lymphoma. Although the exact incidence of transformation is not well defined, it is known to have reduced with modern treatments.
What is it called when you don't respond to your first treatment?
Or sometimes they don't respond well to their first treatment this is known as refractory disease. For patients who have relapsed follicular lymphoma (FL), there are a number other treatments ...
Can follicular lymphoma return?
Although many patients can have a remission that lasts many years after their initial treatment for follicular lymphoma (FL) - the disease will return. In a small number of cases FL can become more acute or transform (change). If this is the case we have outlined different treatment options below.
Can you take part in a clinical trial in Florida?
Taking part in a clinical trial can often be the best option for some FL patients .
