Table 2 Treatment effect and basis of CU case reports
From: Efficacy and safety of compassionate use for rare diseases: a scoping review from 1991 to 2022
No | Drug Name | Disease | Basis of compassionate drug usea | Treatment effect | CU detail |
|---|---|---|---|---|---|
1 | Defibrotide [30] | Hepatic veno-occlusive disease | 1 + 3 | Cure | The patient was an infant under 1 year old and does not meet the clinical trial conditions |
2 | Cinacalcet [31] | Oncogenic osteomalacia | 3 | No significant effect | The patient presented with hypocalcemia due to Cinacalcet’s pharmacological action |
3 | IVb Ribavirin [32] | Severe adenovirus disease | 2 | No significant effect | Intravenous injection is still not approved in the FDA. No AEsc during treatment |
4 | ONC201[33] | Pediatric diffuse intrinsic pontine glioma | 1 | Symptoms improved | No AEs during treatment |
5 | Nivolumab [34] | Pediatric glioblastoma | 6 | Worsened | The patient has Grade 4–5 AE (Brain edema death), and there were reports of AE in other studies |
6 | Miransertib [35] | PIK3CA-related overgrowth syndrome | 1 + 2 + 3 | Symptoms improved | No serious AEs |
7 | Nirogacestat [36] | Desmoid tumors | 1 | Symptoms improved | No serious AEs |
8 | Sunitinib [37] | Metastatic alveolar soft part sarcoma | 2 | No significant effect | Sunitinib has serious skin toxicity, which has been reported in other literatures. The patient presented with necrosis of the skin transplant requiring necrectomy and skin grafting |
9 | Nedosiran [38] | Primary hyperoxaluria 1 | 1 | Symptoms improved | No serious adverse reactions |
10 | Haemonine [39] | Haemophilia B | 3 | Symptoms improved | No serious adverse reactions |
11 | AL101 [40] | Desmoid tumors | 1 | Symptoms improved | Grade 3 diarrhea occurred in both patients; however, this adverse event was short-lived and resolved with dose modification |
12 | Favipiravir [41] | Ebola virus disease | 1 | No significant effect | The effect of treatment was not statistically significant, except for its influence on survival time |
13 | Ruxolitinib [42] | Chronic eosinophilic leukemia | 2 | Symptoms improved | No AEs during treatment |
14 | Bosentan [43] | Buerger disease or thromboangiitis obliterans | 1 | Cure | No AEs during treatment |
15 | Lorlatinib [44] | Inflammatory myofibroblastic tumour | 3 | Symptoms improved | This case demonstrates a role of lorlatinib in the treatment of TPM4-ALK-rearranged IMT despite failure of entrectinib |
16 | Defibrotide [45] | Hepatic Veno-occlusive disease | 2 + 3 | Symptoms improved | Most patients thus had evidence of persistent or intermittent grade 1 or 2 bleeding. Grade 3–4 adverse events during therapy consisted of sepsis; pulmonary edema; CMVd infection; hypotension; etc., but a causative temporal relationship to any grade 3 or 4 toxicity with defibrotide could not be shown |
17 | Bedaquiline [46] | Multidrug-resistant tuberculosis | 1 | Symptoms improved | 19 SAEs were reported in 14 patients |
18 | Gemtuzumab Ozogamicin (GO)e [47] | Acute myeloid leukemia, high-risk myelodysplastic syndrome, or acute promyelocytic leukemia | 1 + 2 | No description | GO was voluntarily withdrawn from the US market in 2010 after a phase III study evaluating GO in combination with chemotherapy in previously untreated adult AML failed to show clinical benefit versus chemotherapy alone |
19 | Imatinib mesylate [48] | Gastrointestinal stromal tumors | 1 | Symptoms improved | After the end of clinical trial of imatinib, the patient continued to apply for medication through CU program |
20 | Human recombinant antithrombin (rhAT)f [49] | Hereditary antithrombin deficiency | 2 + 3 | Symptoms improved | No serious AEs |
21 | Ropeginterferon alpha-2b (Besremi) [50] | Classical Ph (−)g myeloproliferative neoplasms | 1 + 3 | Symptoms improved | Most therapy-related side effects were mild, and there was no treatment discontinuation attributable to intolerable adverse events |
22 | Aflibercept [51] | Colorectal cancer | 1 + 3 | Symptoms improved | No serious AEs |
23 | Hydralazine/Valproate (TRANSKRIP™) [52] | Myelodysplastic syndrome | 1 + 3 | Symptoms improved | No serious AEs |
24 | Polatuzumab Vedotin [53] | Diffuse large B-cell lymphoma | 1 | Symptoms improved | No serious AEs |
25 | Letermovir [54] | Cytomegalovirus infection | 1 | Symptoms improved | Six deaths were reported; The local researchers did not classify it as related to Letemovir, only one case occurred during Letemovir because of grade 4 GVHDh |
26 | Pemetrexed [55] | Peritoneal mesothelioma | 1 | Symptoms improved | The most reported SAEsi for the total expanded access program were dehydration (7.2%), nausea (5.2%), and vomiting (4.9%) |
27 | Recombinant human interleukin 7 (rhIL-7)j [56] | Multifocal leukoencephalopathy | 2 + 3 | Symptoms improved | No AEs during treatment |
28 | Recombinant hirudin [57] | Heparin-induced thrombocytopenia | 3 | Symptoms improved | No AEs during treatment |
29 | Imatinib [58] | Chordoma | 1 + 3 | Symptoms improved | Grade 3–4 AE occurred in 7 of 48 patients |
30 | Fasudil [59] | Amyotrophic lateral sclerosis | 3 + 4 + 5 | Symptoms improved | No AEs during treatment |
31 | Inotuzumab Ozogamicin [60] | B acute lymphoblastic leukemia | 1 + 3 | Symptoms improved | No AEs during treatment |
32 | Lorlatinib [61] | Papillary thyroid cancer | 3 | Symptoms improved | No AEs during treatment |
33 | Gemtuzumab Ozogamicin [62] | CD33 + acute myeloid leukemia | 1 + 3 | Symptoms improved | All 24 treated patients developed grade 3–4 neutropenia and/or thrombocytopenia |
34 | Abiraterone Acetate [63] | Prostate cancer | 1 | Symptoms improved | Most common grade 3 to 4 AE were anemia (13.9%), hypokalemia (7.3%), fatigue (6.8%), and pain (6.3%). Median duration of treatment was 5.3 months (interquartile range: 2.8–10.3). The main study limitation is its retrospective design |
35 | Imatinib [64] | Advanced gastrointestinal stromal tumour | 1 | Symptoms improved | No serious AEs |
36 | Avapritinib [65] | Gastrointestinal stromal tumour | 1 | Symptoms improved | No serious AEs |
37 | Ulixertinib [66] | BRAF D594G cutaneous melanoma | 1 + 3 | Symptoms improved | The patient accessed ulixertinib via an expanded access program (NCT04566393) as she was ineligible for active clinical trials at the time. No serious AEs |
38 | Difluoromethylornithine [67] | Bachmann-Bupp syndrome | 1 + 3 + 4 | Symptoms improved | No AEs during treatment |
39 | Alpelisib [68] | CLOVES syndrome | 2 + 3 + 4 | Symptoms improved | No AEs during treatment |
40 | Risdiplam [69] | Spinal muscular atrophy (SMA)k | 1 + 2 | No description | This article mainly discusses safety of risdiplam. Gastrointestinal disorders were the most common AEs. For patients with SMA1, 30 AEs were reported in 13 cases with 2 serious AEs in 1 patient. For SMA2, 100 AEs were documented in 31 case reports, including 8 serious AEs in 2 patients |
41 | Avapritinib [70] | Mucosal melanoma and thymic carcinoma | 1 + 3 + 5 | Symptoms improved | Case 1: grade 2 vasculitis and grade 2 uveitis occurred, in the absence of predisposing factors. Case 2: grade 2 haematologic toxicity occurred, including anaemia and thrombocytopaenia |
42 | Lumasiran [71] | Primary Hyperoxaluria Type 1 | 1 | Cure | No serious AEs |
43 | Alpelisib [72] | Extensive venous malformations | 1 + 3 + 4 | Cure | No serious AEs |
44 | Avacopan [73] | Antineutrophil Cytoplasmic Antibody–Associated Vasculitis | 1 | Symptoms improved | No AEs during treatment |
45 | Bulevirtide [74] | HDV-related cirrhosis | 1 + 3 | Symptoms improved | No AEs during treatment |
46 | Asfotase Alfa [75] | Childhood Hypophosphatasia | 3 | Symptoms improved | No side effects were observed except for mild injection site reactions (erythema, pain, lipohypotrophy, and lipohypertrophy) |