Bradley McGregor, MD, clinical director of Lank Center for Genitourinary Oncology, senior physician at Dana-Farber Cancer Institute, and instructor of Medicine at Harvard Medical School, discusses the CheckMate-9ER trial (NCT03141177) of nivolumab (Opdivo) plus cabozantinib (Cabometyx) versus sunitinib (Sutent) in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC).

This trial enrolled patients from all of the International Metastatic RCC Database Consortium risk groups. The number of patients in each risk were comparable to real-world practice according to McGregor, with 20% to 25% having favorable risk, about 60% having intermediate risk, and about 20% having poor risk. The patients were evenly distributed through the United States, Europe, and the rest of the world.

The data from the initial analysis showed that there was a marked improvement in progression-free survival (PFS) at a median follow-up of 18 months. This improvement produced a hazard ratio of 0.51, with a median PFS of 16.6 months with the combination versus 8.3 months with sunitinib. The overall survival has not been reached in either group, but the hazard ratio favors the combination at 0.60. McGregor says the P value was also statistically significant. The subgroups also favored nivolumab and cabozantinib in this study.

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Videos

Bradley McGregor, MD, discusses the CheckMate-9ER trial of nivolumab plus cabozantinib versus sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma.

CheckMate-9ER Shows Efficacy of Nivolumab/Cabozantinib Combo in RCC

Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses potential upcoming treatment options for patients with mantle cell lymphoma (MCL), including targeted therapies and chimeric antigen receptor (CAR) T cells.

These treatments include LOXO-305, which Wang says is very effective and will probably be another addition to the therapeutic options in the near future. It is able to reverse Bruton’s tyrosine kinase (BTK) inhibition, similar to the other 3 approved BTK inhibitors which are all reversible, such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa).

Wang believes the treatment of MCL has evolved from chemotherapy regimens like rituximab (Rituxan), cyclophosphamide, doxorubicin, and vincristine (R-CHOP) and rituximab plus bendamustine to a targeted therapy and CAR T-cell therapy era.

Brexucabtagene autoleucel (Tecartus), a CAR T agent, being approved is only the beginning for patients with MCL, according to Wang. Many other CAR T-cell studies are being designed for this setting with different mechanisms of action, including on and off switches, peptide insertions, and PD-L1 knockout.

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Michael Wang, MD, discusses potential upcoming treatment options for patients with mantle cell lymphoma, including targeted therapies and chimeric antigen receptor T cells.

Exploring Targeted and CAR T-Cell Therapies on the Horizon for MCL

Case Impressions: A 73-Year-Old Woman With DTC

Recommendations for Treating Patients With DTC

Systemic Therapy for RAI-Refractory DTC

Lenvatinib Data for RAI-Refractory DTC

Real-World Insight: Lenvatinib for RAI-Refractory DTC

Progress in Treating RAI-Refractory DTC

Case: A 73-Year-Old Woman With Differentiated Thyroid Cancer

A 73-year-old woman complains of a “lump” on her neck, with occasional swelling and dysphagia

Ultrasound of the neck revealed a 3.0 cm mass in the right lobe of the thyroid; several suspicious lymph nodes ranging from 0.2-3.0 cm in size

Ultrasound-guided FNAB: confirmed papillary thyroid carcinoma

Patient underwent total thyroidectomy with bilateral central neck dissection

Pathology: 3.0 cm papillary thyroid cancer arising in right lobe of the thyroid, 2 of 5 positive central compartment lymph nodes, largest 1.4 cm, positive extra nodal extension

Levothyroxine to suppression was added to treatment regimen

Follow-up at 6 months TSH 0.4 µU/mL, thyroglobulin 4 ng/mL

Follow-up 12 months TSH 0.3 µU/mL, thyroglobulin 18 ng/mL

CT of the chest showed 10 lung nodules, largest 1.2 cm in size

Administered radioactive iodine 150 millicuries

Post therapy scan showed no lung or other uptake

Follow-up at 2 years TSH 0.3 µU/mL, thyroglobulin 30 ng/mL

Chest CT increasing number and size of lung nodules; largest 1.6 cm

Patient was asymptomatic and deemed radioactive iodine refractory

Systemic therapy with lenvatinib 24 mg PO qDay considered

Andrew G. Gianoukakis, MD, of Harbor-UCLA Medical Center, describes the rationale for treating a patient with RAI-refractory differentiated thyroid cancer with systemic therapy.

A 73-Year-Old Woman With Differentiated Thyroid Cancer

Case Overview: 77-Year-Old Woman With DLBCL

Approaching DLBCL: Risk Assessment and Prognosis

DLBCL: Cytogenetic Testing and Treatment Initiation

Frontline Treatment Approaches in DLBCL

Current Treatment Approaches for R/R DLBCL

Implications for Treating R/R DLBCL With the L-MIND Regimen

R/R DLBCL: Observations From the Re-MIND Study

R/R DLBCL: Treating With Tafasitamab Plus Lenalidomide

Progress Made in Treating R/R DLBCL

A 77-year-old woman presented with loss of appetite, fatigue and shortness of breath

PMH: post-menopausal; DM, medically controlled

PE: palpable inguinal lymphadenopathy; splenomegaly

Core needle biopsy of the inguinal node: CD20-positive diffuse large B-cell lymphoma, non-GCB subtype. FISH panel: t(14;18) with a BCL2 rearrangement; no MYC or BCL6 rearrangement

Whole body PET/CT scan showed FDG avidity the inguinal lymph node region, largest node 3.3 cm; splenomegaly; and a small suspicious lung lesion

Bone marrow biopsy: involvement with DLBCL

Conclusion: stage IV DLBCL, non-GCB subtype

IPI score high-risk; CNS relapse score intermediate risk

End-of-treatment PET/CT demonstrates a Deauville 2 complete remission

1 year later while in surveillance she presents with new cervical, axillary, mediastinal, and abdominal lymphadenopathy

Core needle biopsy of an axillary node confirms a relapse of DLBCL, non-GCB subtype

Based on her age of 78 years and performance status, you consider her to be transplant-ineligible

You elect to initiate tafasitamab + lenalidomide

John M. Burke, MD, of Rocky Mountain Cancer Centers, explains the rationale behind treating an elderly woman with relapsed diffuse large B-cell lymphoma with tafasitamab and lenalidomide after R-CHOP chemotherapy.

A 77-Year-Old Woman with DLBCL

Randall A. Oyer, MD, medical director at the Ann B. Barshinger Cancer Institute of Penn Medicine Lancaster General in Pennsylvania, and current president of the Association of Community Cancer Centers (ACCC), discusses the importance of the ACCC community during the unprecedented coronavirus disease 2019 (COVID-19) pandemic.

The pandemic crystalized the importance of community, at home, in the professional setting, and the bigger community known as ACCC, says Oyer. When something unknown happens, we look for precedent, but there was none for this scenario. Members leaned on each other for support, however, during these new and challenging times.

Colleagues within the ACCC community who were at the forefront of the pandemic in areas such as Seattle and New York were able to share their experiences with the community to show what they have done, what they have tried, and what they have learned, Oyer says. Whether physicians interact via programs, blogs, written material, or during physical meetings, physicians in the ACCC community are readily available to help each other in times of need, which is what Oyer believes the community is about.

Randall A. Oyer, MD, discusses the importance of the ACCC community during the unprecedented coronavirus disease 2019 pandemic.

ACCC President Highlights Oncology Community Response to COVID-19 Pandemic

Phase 2 L-MIND Trial Overview

RE-MIND Comparison Data Review

L-MIND and RE-MIND Practical Implications

A key opinion leader provides an overview of emerging data for a promising CD-19 targeted therapy and discusses how it has impacted the treatment paradigm.

Targeting CD19 in Diffuse Large B-Cell Lymphoma: Treatment Updates

Christine Dierks, MD, senior physician at the University Hospital Freilburg in Germany, discusses the early data from a study looking at the combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) in patients with metastatic anaplastic or poorly differentiated thyroid carcinoma.

This trial was the same drug combination and patient population as the phase 2 ATLEP study that Dierks was a part of. Similarly, patients had previously treated disease with multiple therapies, such as chemotherapy, except for lenvatinib and pembrolizumab.

At the European Society of Medical Oncology (ESMO) Virtual Congress 2020, the data for the first 20 patients after 3 months was presented and the rest will not come out for a long period of time, according to Dierks. The response rate after 3 months was 30% and the best overall for patients was 50%, including some patients who are 9 months into the regimen. She says the overall response is slowly improving over time as patients go further on therapy.

The time to response with the combination is slow and complete remission rates were seen in 8 patients and the first complete remission was seen after 11 months of treatment. Dierks believes that patients have to stay on therapy for a long period of time to achieve complete response.

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Christine Dierks, MD, discusses the early data from a study looking at the combination of lenvatinib and pembrolizumab in patients with metastatic anaplastic or poorly differentiated thyroid carcinoma.

Early Data Presented for Lenvatinib and Pembrolizumab in Thyroid Cancer

Presentation of a Patient With Diffuse Large B-Cell Lymphoma

Initial Treatment of Diffuse Large B-Cell Lymphoma

Results of the L-MIND Clinical Trial

L-MIND Trial Regimen Overview

Novel Treatment Options in Diffuse Large B-Cell Lymphoma

Case: A 74-Year-Old Man with Diffuse Large B-Cell Lymphoma

A 74-year-old man presented with fever, 14-lb unintentional weight loss and occasional chest pain

PE: tired-appearing man; palpable bilateral cervical lymphadenopathy



Labs: LDH 2 times above normal; Hb 10.8 g/dL; bilirubin 2.3 mg/dL; creatinine 1.7 mg/fl; all others WNL

Lymph node biopsy; CD 20+ confirmed DLBCL; IHC panel: CD 10+, CD 19+

Whole body PET/CT scan showed activity the cervical lymph node region, largest node 2.5 cm; evidence of axillary and thoracic subcutaneous tissue involvement

Ann Arbor stage 4; IPI: high-risk; ECOG PS 1

Treatment initiated with R-CHOP + RT; well-tolerated

Interim PET scan after 4 cycles; progressive diseases noted

Due to transplant ineligibility patient was treated with tafasitamab + lenalidomide

Gilles Salles, MD, reviews the case of a 74-year-old man with diffuse large B-cell lymphoma.

A 74-Year-Old Man With Diffuse Large B-Cell Lymphoma

Kami J. Maddocks, MD, associate professor of clinical internal medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center–James, discusses the role of tafasitamab (Monjuvi) and lenalidomide (Revlimid) following the approval of this agent as treatment of patients with relapsed/refractory diffuse large B-cell lymphoma.

For patients who are ineligible for salvage chemotherapy followed by transplant, this combination was approved for the treatment of patients after first relapse. Historically, physicians would provide some sort of palliative chemotherapy in this setting if the patient was a candidate and was pursuing therapy or had consideration of clinical trial, but this is the only approved agent in this setting, Maddocks says.

The overall response rate in the phase 2 study that led to the combination’s approval was 60% with a complete response rate of 40%. The median progression-free survival was a little over 1 year, and the median overall survival was not reached in the initial dataset. With further follow-up, though, Maddocks says the median duration of response was nearly 3 years. This is an impressive finding, that patients achieve durable responses with the combination.

Kami J. Maddocks, MD, discusses the role of tafasitamab and lenalidomide following the approval of this agent as treatment of patients with relapsed/refractory diffuse large B-cell lymphoma.

Tafasitamab Plus Lenalidomide Approval Generates Excitement for Second-Line DLBCL

Case Overview: 58-Year-Old Man With Advanced RCC

Risk Stratification of Patients With Advanced RCC

Advanced RCC Treatment Selection

Second-Line Treatment Options for Advanced RCC

Lenvatinib and Everolimus for Advanced RCC

Novel Therapies in Advanced RCC

Case: A 58-Year-Old Man With Advanced Renal Cell Carcinoma

August 2018: A 58-year-old man complained of fatigue and anorexia; after appropriate workup the patient was diagnosed with clear cell renal cell carcinoma

March 2019: He developed metastatic disease to the lungs bilaterally (30 x 35 mm), mediastinum and soft tissue metastatic deposits

He was started on pembrolizumab 200 mg IV every 21 days + axitinib 5 mg PO q2Days

September 2019: He developed progressive disease (45 x 50 mm); pulmonary lymph nodes increased in size and new mediastinal and hilar lymphadenopathy was noted

He was started on lenvatinib 18 mg PO qDay + everolimus 5 mg PO qDay

October 2019: Due to grade 1 diarrhea, reduced dose of lenvatinib to 14 mg PO qDay + everolimus 5 mg PO qDay

December 2019: Lesions reduced to 20 x 20 mm from September 2019; achieved partial response

January 2020: He remained on therapy with lenvatinib + everolimus

Robert Alter, MD, of John Theurer Cancer Center, describes the rationale for treating a 58-year-old male with advanced renal cell carcinoma with the combination of lenvatinib and everolimus following progression on first-line therapy.