What is the prognosis for Non-Hodgkin Lymphoma (NHL)?

From the Guidelines

The prognosis for Non-Hodgkin lymphoma (NHL) is generally favorable, with a 5-year survival rate of approximately 70% across all types, and recent advances in treatment approaches have significantly improved outcomes for many NHL subtypes over the past decades. The prognosis varies widely depending on several factors including the specific subtype, stage at diagnosis, patient age, and response to treatment [ 1 ]. Indolent (slow-growing) lymphomas like follicular lymphoma typically have better long-term survival rates but are often not curable, while aggressive lymphomas such as diffuse large B-cell lymphoma (DLBCL) can be cured with appropriate treatment in many cases.

Key Factors Influencing Prognosis

• The specific subtype of NHL, with follicular lymphoma being the second most common lymphoid malignancy, representing 20% to 25% of all cases of non-Hodgkin’s lymphoma (NHL) [ 1 ]
• Stage at diagnosis, with early-stage disease having a better prognosis than advanced-stage disease [ 1 ]
• Patient age, with older patients generally having a poorer prognosis than younger patients [ 1 ]
• Response to treatment, with patients who respond well to initial treatment having a better prognosis than those who do not [ 1 ]

Treatment Approaches

• Chemotherapy regimens such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for B-cell lymphomas [ 1 ]
• Radiation therapy, stem cell transplantation, targeted therapies, and immunotherapies depending on the specific diagnosis [ 1 ]
• Regular follow-up care is essential after treatment, as some patients may experience relapse requiring additional therapy [ 1 ]

Prognostic Tools

• The International Prognostic Index (IPI) is commonly used to predict outcomes, considering factors like age, disease stage, LDH levels, performance status, and extranodal involvement [ 1 ]
• The FLIPI (Follicular Lymphoma International Prognostic Index) and FLIPI2 are used to predict outcomes in follicular lymphoma [ 1 ]
• The m7-FLIPI, which incorporates mutational analysis of seven genes along with clinical risk factors, has been developed to improve prognostication in follicular lymphoma [ 1 ]

From the FDA Drug Label

The main outcome measure of the study was progression-free survival, defined as the time from randomization to the first of progression, relapse, or death Among all enrolled patients, 62% had centrally confirmed DLBCL histology, 73% had Stage III–IV disease, 56% had IPI scores greater than or equal to 2,86% had ECOG performance status of < 2,57% had elevated LDH levels, and 30% had two or more extranodal disease sites involved Efficacy results are presented in Table 15. Table 15 Efficacy Results in NHL Studies 7,8, and 9 Study 7(n = 632) Study 8(n = 399) Study 9(n = 823) R-CHOPCHOPR-CHOPCHOPR-ChemoChemo Main outcomeProgression-free survival(years)Event-free survival(years)Time to treatment failure(years)

• NE = Not reliably estimable. † R-CHOP vs. CHOP. ‡ Significant at p < 0.05,2-sided. § Kaplan-Meier estimates. Median of main outcome measure3.11.62.91. 1NENE Hazard ratio†0.69‡0.60‡0.45‡ Overall survival at 2 years§74%63%69%58%95%86% Hazard ratio†0.72‡0.68‡0.40‡

The prognosis for Non-Hodgkin lymphoma (NHL) patients, specifically those with Diffuse Large B-Cell Lymphoma (DLBCL), can be estimated based on the provided efficacy results from NHL Studies 7,8, and 9.

• The median progression-free survival for patients treated with R-CHOP was 3.1 years in Study 7, and the hazard ratio was 0.69, indicating a significant improvement in progression-free survival compared to CHOP alone.
• The overall survival at 2 years was 74% for R-CHOP and 63% for CHOP in Study 7, with a hazard ratio of 0.72.
• In Study 8, the overall survival estimates at 5 years were 58% for R-CHOP and 46% for CHOP. The prognosis varies depending on the specific patient population and treatment regimen. Key factors that influence prognosis include:
• IPI scores: 56% of patients had IPI scores greater than or equal to 2.
• ECOG performance status: 86% of patients had an ECOG performance status of < 2.
• LDH levels: 57% of patients had elevated LDH levels.
• Extranodal disease sites involved: 30% of patients had two or more extranodal disease sites involved. 2

From the Research

Non-Hodgkin Lymphoma Prognosis

• The prognosis for non-Hodgkin lymphoma (NHL) patients depends on various factors, including the subtype of lymphoma, stage of disease, and response to treatment 3, 4.
• The International Prognostic Index is used to define prognostic subgroups, and molecular and genetic markers of prognosis may be used to further refine treatment decisions 3.
• For patients with follicular lymphomas, treatment with radiation therapy is generally used for early-stage disease, while chemotherapy, immunotherapy, or radioimmunotherapy is used for stage III and IV disease 3.
• Patients with diffuse large B-cell lymphoma (DLBCL) may receive doxorubicin-based chemotherapy combined with rituximab, followed by involved field radiation therapy for limited-stage disease, or rituximab combined with chemotherapy alone for extensive disease 3.
• Consolidation radiation therapy (RT) has been shown to improve outcomes for patients with advanced DLBCL, particularly in cases with initially bulky disease, bone involvement, or partial response to systemic therapy 5.

Factors Affecting Prognosis

• Several factors have been identified as predictors of outcome for NHL patients, including follicular histology, prior autologous bone marrow transplantation, lack of bone marrow involvement or extranodal disease, and low/normal serum lactate dehydrogenase (LDH) or beta2 microglobulin 6.
• However, some factors associated with prognosis following chemotherapy may not correlate with response to rituximab or response duration 6.
• The follicular lymphoma international prognostic index (FLIPI) did not consistently correlate with response to rituximab or response duration 6.

Emerging Treatments

• Immunotherapy, including immune checkpoint blockade, bispecific antibodies, and chimeric antigen receptor T cells, has shown promise in treating relapsed/refractory lymphomas 7.
• These treatments have the potential to transform treatment paradigms across many lymphoma subtypes, but further research is needed to understand their mechanisms of action, toxicity, and resistance 7.