New Strategies in SCLC and DLBCL Are Transforming the Treatment Landscape

Small cell lung cancer (SCLC) and diffuse large B-cell lymphoma (DLBCL) are aggressive malignancies that pose significant challenges due to their high prevalence and complex treatment landscapes. SCLC, heavily associated with smoking, accounts for a notable proportion of lung cancer cases worldwide, while DLBCL represents the most common subtype of non-Hodgkin lymphoma. Both conditions demand innovative therapeutic approaches as they often present at advanced stages, complicating management and impacting survival rates. However, recent advancements in treatments, including immunotherapies and targeted therapies, are transforming patient outcomes across the globe.

SCLC is a progressive subtype of lung cancer that accounts for around 10% to 15% of all lung cancer cases that are diagnosed globally. According to a news release, an estimated 400,000 new cases of SCLC are documented, with Asia reporting the highest number of cases at 63%, followed by Europe and North America—emphasizing the importance of region-specific trials and recruitment strategies.¹ Smoking tobacco is the leading risk factor of developing SCLC, and accounts for 98% of all cases.²

DLBCL is an aggressive subtype of non-Hodgkin lymphoma, accounting for 30% to 40% of all non-Hodgkin lymphoma cases.³ Differing from Hodgkin lymphoma, non-Hodgkin is more common and spreads to other parts of the body, as Hodgkin is typically confined to lymph nodes of the neck, chest, or under arms and is more curable.⁴ However, individuals treated for Hodgkin’s lymphoma have an increased risk of developing lung cancer. The risk increases among individuals treated at age 45 or older and among individuals that smoke.⁵

Image credit: Konstantin Yuganov | stock.adobe.com

Following a diagnosis, SCLC is divided into limited-stage and extensive stage, which is classified by how much the disease has spread.² If found in the extensive-stage, the 5-year survival rate is less than 5%, compared to 15-25% if detected in the limited stage.¹ However, because SCLC grows and spreads at a rapid rate, around 60% of cases are found when the cancer has already metastasized to other parts of the body—including the liver, bones, brain, and adrenal glands.^1,2

As of 2022, an estimated 194,000 news cases of DLBLC were diagnosed globally, with Asia accounting for the largest number of cases. DLBLC is divided into 2 molecular subtypes, germinal center B-cell-like (GCB) and activated B-cell-like (ABC). The study authors noted that individuals with ABC have a lower 3-year progression-free survival rate as GCB typically has a better prognosis.³

Advancements in SCLC

In terms of treatment options for SCLC, therapies vary depending on the stage and treatment history for each individual. Recommended first-line therapies for limited-stage SCLC includes platinum-based chemotherapy with radiotherapy, as treatment for extensive-stage SCLC includes platinum-based chemotherapy plus immunotherapy, followed by maintenance. Additionally, treatment for relapsed or refractory (R/R) cases includes lurbinectedin (Zepzelca, Pharma Mar SA) or topotecan (Hycamtin; Pfizer), or alternatively enrollment in clinical trials investigating other therapeutic options.¹

A research report highlighted that current key treatment options for SCLC include pipeline drugs like immune checkpoint inhibitors, such as pembrolizumab (Keytruda; Merck) and nivolumab (Opdivo; Bristol Myers Squibb), which act by targeting PD-1/PD-L1. Topotecan and lurbinectedin are other small molecules that play a significant role in treatment outcomes, according to the report.¹

As of 2019, around 1200 clinical trials focused on SCLC have been initiated, with leads in the number of clinical trials beginning with Asia-Pacific, North America, and Europe. A research report noted that results emerging from phase 3 trials demonstrated positive findings with immunotherapies such as nivolumab and serplulimab (Hansizhuang; Shanghai Henlius Biotech) and antibody drug conjugates such as ifinatamab deruxtecan (DS-7300; Daiichi Sankyo and Merck & Co, Inc), which have all provided advancements in SCLC treatment.¹

“These strategies are transforming the treatment landscape, offering new hope for R/R cases. While some aspects of SCLC biology remain unclear, ongoing research is continuously refining targeted treatments and improving outcomes for patients,” wrote the authors of the report.¹

Advancements in DLBCL

Recommended guidelines from 2024 suggested treatment with first-line regimens such as rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate (Oncovin; Eli Lilly and Company), and prednisone (R-CHOP) and polatuzumab vedotin (Polivy; Genentech), rituximab, cyclophosphamide, doxorubicin hydrochloride, and prednisone (pola-R-CHP) to aid DLBCL outcomes, however, treatments differ depending on the disease state, patient condition, and treatment history. Individuals diagnosed in the advanced stage or R/R cases could be treated with CAR-T cell therapy or glofitamab (Columvi; Genentech)—a bi-specific antibody.³

A research report provided that as of 2019, more than 1500 clinical trials focusing on treatment for DLBCL have been introduced globally. Asia-Pacific leads with 41% of clinical trials, followed by North America with 33%, and Europe with 19%. The authors of the report noted that the initiation of the clinical trials emphasize the importance of finding new and improved treatment options for DLBCL.³

Expanding from traditional chemotherapies to treat DLBCL, a research report noted that targeted therapies and immunotherapies have been explored in these clinical trials, demonstrating promising outcomes. Specifically, phase 3 trials evaluating mosunetuzumab (Lunsumio; Genentech, Inc) and selinexor (Xpovio; Karyopharm Therapeutics Inc) displayed positive results for individuals with R/R DLBCL. Additionally, CAR T-cell therapies and checkpoint inhibitors demonstrated strong efficacy in individuals at high risk of DLBCL that did not response to R-CHOP, according to the report.³

“While many genetic mutations remain unclear, ongoing research is identifying new targets, driving the development of more effective and personalized treatment options,” wrote the authors of the report.³

REFERENCES

1. Small Cell Lung Cancer: Global Clinical Trial Landscape (2024). Novotech. News release. October 18, 2024. Accessed November 27, 2024. https://novotech-cro.com/reports/small-cell-lung-cancer-global-clinical-trial-landscape-2024?utm_source=BusinessWire&utm_medium=Press+Release&utm_campaign=2024_Sep_SCLC_DR_EN&utm_id=701Oc00000Cya6aIAB.

2. Small Cell Lung Cancer. Yale Medicine. News release. Accessed November 27, 2024. https://www.yalemedicine.org/conditions/small-cell-lung-cancer#:~:text=There%20are%20two%20primary%20forms,and%20improving%20quality%20of%20life.

3. Diffuse Large B-Cell Lymphoma- Global Clinical Trial Landscape (2024). Novotech. News release. October 3, 2024. Accessed November 27, 2024. https://novotech-cro.com/reports/diffuse-large-b-cell-lymphoma-global-clinical-trial-landscape-2024?utm_source=BusinessWire&utm_medium=Press+Release&utm_campaign=2024_Oct_DLBCL_DR_EN&utm_id=701Oc00000CyZ5eIAF.

4. Hodgkin's vs. non-Hodgkin's lymphoma: What's the difference? Mayo Clinic. News release. January 10, 2023. Accessed November 27, 2024. https://www.mayoclinic.org/diseases-conditions/hodgkins-lymphoma/expert-answers/lymphoma/faq-20058546#:~:text=The%20difference%20between%20Hodgkin's%20lymphoma%20and%20non%2DHodgkin's%20lymphoma%20can,getting%20the%20care%20you%20need.&text=With-,Rajiv,Pruthi%2C%20M.B.B.S.

5. Lung cancer after treatment for Hodgkin's lymphoma: a systematic review. National Library of Medicine. October 6, 2005. Accessed November 27, 2024. https://pubmed.ncbi.nlm.nih.gov/16198983/#:~:text=Abstract,and%20proteomic%20assessment%20is%20planned.