Single-Agent Immunotherapy for Two Types of Cancer in One Patient

Musher, Benjamin; Rahal, A.

doi:10.7326/l18-0360

Cited by 5 publications

(7 citation statements)

References 5 publications

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“…In summary, 10 cases were included with a colorectal cancer (three with multiple cancers in other organs as well) and one patient with liver metastases from a previously removed colorectal cancer. 18,24,26,28,29,[34][35][36][37][38] Two cases obtained CR, two showed PR, three had SD, and three showed PD giving an ORR of 40% and disease control rate of 70%. All the patients, who showed positive response, were given immunotherapy as first (N=3) or second (N=1) line treatment.…”

Section: Colorectal Cancermentioning

confidence: 96%

“…Investigating noncolorectal cancers, 21 MSI/dMMR Lynch syndrome-associated solid tumors developed (three glioblastoma multiforme, four pancreatic cancers, three ureteral cancers, two lung cancers, two prostate cancers, two adrenocortical carcinomas, two bladder cancers, one endometrial cancer, one rhabdomyosarcoma, and one intrahepatic cholangiocarcinoma). 18,[22][23][24]26,34,[38][39][40][41][42][43][44][45][46][47][48][49] Although it was not stated, it was considered highly likely that the pancreatic cancer showing PD at 22 months by Hu et al, 49 was included in the large pancreatic cancer cohort study. 33,49 However, in order to reduce publication bias, this case was included in the following summary.…”

Section: Noncolorectal Cancermentioning

confidence: 99%

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An Update on Immune Checkpoint Therapy for the Treatment of Lynch Syndrome

Therkildsen¹,

Jensen

Rasmussen³

et al. 2021

CEG

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During the recent years, immune checkpoint-based therapy has proven highly effective in microsatellite instable (MSI) solid tumors irrespective of organ site. MSI tumors are associated with a defective mismatch repair (MMR) system and a highly immune-infiltrative tumor microenvironment—both characteristics of Lynch syndrome. Lynch syndrome is a multi-tumor syndrome that not only confers a high risk of colorectal and endometrial cancer but also cancer in, eg the upper urinary tract, ovaries, and small bowel. Since the genetic predisposition for Lynch syndrome are pathogenic variants in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2 , most of the Lynch syndrome cancers show MMR deficiency, MSI, and activation of the immune response system. Hence, Lynch syndrome cancer patients may be optimal candidates for immune checkpoint-based therapies. However, molecular differences have been described between sporadic MSI tumors (developed due to MLH1 promoter hypermethylation) and Lynch syndrome tumors, which may result in different treatment responses. Furthermore, the response profile of the rare Lynch syndrome cases may be masked by the more frequent cases of sporadic MSI tumors in large clinical trials. With this review, we systematically collected response data on Lynch syndrome patients treated with FDA- and EMA-approved immune checkpoint-based drugs (pembrolizumab, atezolizumab, durvalumab, avelumab, ipilimumab, and nivolumab) to elucidate the objective response rate and progression-free survival of cancer in Lynch syndrome patients. Herein, we report Lynch syndrome-related objective response rates between 46 and 71% for colorectal cancer and 14–100% for noncolorectal cancer in unselected cohorts as well as an overview of the Lynch syndrome case reports. To date, no difference in the response rates has been reported between Lynch syndrome and sporadic MSI cancer patients.

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Section: Colorectal Cancermentioning

confidence: 96%

Section: Noncolorectal Cancermentioning

confidence: 99%

An Update on Immune Checkpoint Therapy for the Treatment of Lynch Syndrome

Therkildsen¹,

Jensen

Rasmussen³

et al. 2021

CEG

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“…Few cholangiocarcinoma cases have reported response to pembrolizumab; however, these tumors were microsatellite unstable or mismatch repair genes (MMR) deficient and only one case achieved pCR with pembrolizumab treatment alone [15][16][17][18]. Conversely, our patient was pMMR and MSS but TMB-H. TMB has emerged as an independent predictive biomarker for response to pembrolizumab monotherapy in patients with previously treated, recurrent, or metastatic advanced solid tumors [19,20].…”

Section: Discussionmentioning

confidence: 67%

Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in a Patient With Metastatic Intrahepatic Cholangiocarcinoma With High Tumor Mutational Burden

Abudalou¹,

Vega²,

Kondratiev³

et al. 2021

Cureus

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Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary tract cancer (BTC) with distinct anatomic, molecular, and clinical characteristics. Over the last 10-20 years, ICC has become the focus of increasing concern largely due to its rising incidence and high mortality rates in various parts of the world, including the United States.Surgery is the only potentially curative treatment option for ICC; however, recurrence rate is high, and prognosis is poor in patients with recurrent disease. The chemotherapy regimen of gemcitabine-cisplatin (GemCis) is still the standard of care for patients with unresectable metastatic ICC. There is limited data regarding pathologic ICC response to palliatively intentioned systemic treatment.Here, we report a case of a 47-year-old Caucasian male with metastatic ICC microsatellite stable (MSS) and TMB 49 mutation per megabase who achieved complete pathological response with sequential GemCis/nabpaclitaxel and pembrolizumab. This case highlights the effect of sequential neoadjuvant chemoimmunotherapy in a patient with high tumor mutational burden (TMB-H) ICC, emphasizing the importance of molecular testing, which provides valuable information that can be used in clinical practice to better select targeted chemotherapy regimens.

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“…Yamada et al [13] reported two cases with effective outcomes of pembrolizumab monotherapy (lung + bladder cancer and lung + gastric cancer). Musher and Rahal [14] also described a case of mismatch repair-deficient cancer (Lynch syndrome) presenting with synchronous colon and intrahepatic cholangiocarcinoma that showed CR with pembrolizumab. In contrast to these reports, both co-existing tumors in the present study failed to show simultaneous responses to initial pembrolizumab treatment.…”

Section: Discussionmentioning

confidence: 99%

Initial Therapeutic Approach with Pembrolizumab in Synchronous Multiple Cancers, Including Non-Small Cell Lung Cancer, Highly Positive for Programmed Death-Ligand 1 Expression

et al. 2022

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Treatment of synchronous multiple primary cancers is clinically difficult. We report four cases of synchronous primary cancers, including advanced and metastatic non-small cell lung cancer (NSCLCs) highly positive for programmed death-ligand 1 (PD-L1) expression and initially treated with pembrolizumab. Pembrolizumab was efficacious in two patients with NSCLC lesions, followed by chemoradiotherapy for esophageal cancer (case 1) and chemotherapy for gastric cancer (case 2). Both cancers in case 1 showed a complete response for 3 years, while progression of the accompanying gastric cancer resulted in mortality at 20 months in case 2. Both NSCLC and gastric cancer in case 3 failed to respond to pembrolizumab, but the accompanying laryngeal cancer in case 4 showed a complete response, and cytotoxic chemotherapy for NSCLC was continued for 18.0 months. Our clinical experience suggests that pembrolizumab is a useful therapeutic approach for patients with synchronous cancers, including NSCLC that highly expresses PD-L1.

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Single-Agent Immunotherapy for Two Types of Cancer in One Patient

Cited by 5 publications

References 5 publications

An Update on Immune Checkpoint Therapy for the Treatment of Lynch Syndrome

An Update on Immune Checkpoint Therapy for the Treatment of Lynch Syndrome

Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in a Patient With Metastatic Intrahepatic Cholangiocarcinoma With High Tumor Mutational Burden

Initial Therapeutic Approach with Pembrolizumab in Synchronous Multiple Cancers, Including Non-Small Cell Lung Cancer, Highly Positive for Programmed Death-Ligand 1 Expression

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