A case report of total epidermal necrosis following mirvetuximab soravtansine extravasation

Highlights

• •First reported case of mirvetuximab soravtansine extravasation causing total epidermal necrosis.
• •Indicates the drug's potent payload can cause non-specific injury to healthy skin if it leaks from the vein during treatment.
• •Shows the value of central access and multidisciplinary care in managing drug-related soft tissue injury.

Abstract

Background

Mirvetuximab soravtansine (MIRV) is an antibody–drug conjugate (ADC) approved for the treatment of platinum-resistant ovarian cancer. We report the first known case of total epidermal necrosis secondary to MIRV extravasation, representing an unreported adverse event.

Case

A 74-year-old woman with recurrent high-grade serous carcinoma of the peritoneum who developed extensive soft tissue injury following peripheral intravenous extravasation of MIRV. Despite immediate cessation of the MIRV infusion and conservative management, the patient developed progressive cutaneous toxicity, including full-thickness epidermal necrosis, requiring an 18-day hospitalization and wound care at a regional burn center. No surgical intervention was required. Management included topical therapies, reduced dressing changes, systemic antibiotics, and vitamin D3. Following discharge, a central venous access device was placed, and she completed subsequent MIRV cycles without further complications.

Conclusion

This case underscores the potential for severe soft tissue injury from MIRV extravasation, despite its lack of vesicant labeling. Contributing factors may include the instability of its disulfide linker and the cytotoxicity of the DM4 payload. As MIRV and other ADCs become more widely used in clinical settings, establishing clear protocols for recognizing and managing extravasation is essential. Central venous access and standardized documentation may mitigate risk. Increased awareness and reporting are needed to inform clinical guidelines and ensure safe administration of ADC therapies.

1. Introduction

Epithelial ovarian cancers are among the leading causes of gynecologic cancer-related deaths worldwide (American Cancer Society, 2025). These cancers often present at an advanced stage, and while patients may achieve remission with platinum-based chemotherapy and surgery, approximately 80 % experience recurrence and ultimately develop resistance to platinum-based treatment. Targeted therapies such as ADCs offer a promising treatment option for patients with platinum resistant disease (Davis et al., 2014).

ADCs are novel therapies that enable chemotherapeutic agents to selectively target overexpressed antigens in cancer cells. Approved in 2022, Mirvetuximab Soravtansine (MIRV) is an ADC used to treat platinum-resistant ovarian, fallopian tube, or peritoneal cancers in patients whose tumors express folate receptor alpha (FRα) overexpression (Moore et al., 2023). Its mechanism of action involves a monoclonal antibody targeting FRα receptor and delivering cytotoxic N2′-deacetyl-N2′-(4-methyl-N-piperazinyl) maytansine-1 (DM4), an anti-tubulin agent. Upon internalization, DM4 accumulates within the cancer cell, disrupting microtubule function, inducing antimitotic activity, and ultimately leading to cell death. Notably, these catabolites can also diffuse across cell membranes, enabling the destruction of neighboring cells—a phenomenon known as the bystander effect. The randomized phase III MIRASOL trial demonstrated the superiority of MIRV over investigator’s-choice of chemotherapy in patients with FRα positive, platinum resistant ovarian cancer. Among 453 participants, MIRV significantly improved progression-free survival (5.6 vs. 4.0 months) and overall survival (16.5 vs. 12.7 months), supporting its accelerated Federal Drug Administration’s (FDA) approval. Reported toxicities were primarily ocular and gastrointestinal, with no dermatologic or extravasation events noted—highlighting the rarity of this case.

Extravasation is the unintended leakage of intravenous (IV) drugs into surrounding soft tissue, which can cause pain, swelling, and, in severe cases, tissue necrosis (Kim et al., 2020). Agents classified as vesicants carry the highest risk of damage. Soft tissue injuries related to ADCs have been rarely reported, likely due to their recent adoption in clinical practice (Pipitone et al., 2025). While MIRV-related soft tissue injury was not observed in clinical trials, we report a case of MIRV-associated extravasation injury.

2. Case

A 74-year-old woman with stage IIIC high-grade serous carcinoma of the peritoneum and a medical history of chronic kidney disease stage 3, hypertension, and hypothyroidism was initially treated in Colombia with neoadjuvant carboplatin, paclitaxel, and bevacizumab, followed by optimal debulking surgery. After disease progression, she received carboplatin and doxorubicin, again followed by maintenance bevacizumab. In 2025, after further progression, she began treatment with MIRV in combination with bevacizumab. Treatment selection was guided by + 2 immunohistochemistry demonstrating 50 % folate receptor alpha (FRα) expression. She tolerated the first MIRV cycle without complications.

During cycle 2 of her MIRV/bevacizumab infusion, extravasation was observed approximately 20 min into the MIRV infusion at the intravenous (IV) access site in the left medial cubital vein. The infusion was immediately stopped, the IV line was removed, an ice pack was applied, and her right arm was elevated. A new IV was established in the contralateral right medial cubital vein, and the MIRV infusion was completed. The subsequent bevacizumab infusion was administered without complication. The day after, the patient called with complaints of pain in her arm (Fig. 1, A). Three days later, she presented to an outside hospital with arm pain, erythema, and chills. A venous duplex ultrasound of her right upper extremity (RUE) showed no evidence of deep vein thrombosis or superficial thrombophlebitis. She was admitted for presumed cellulitis and started on IV cefazolin and treated with topical aluminum acetate dressings. However, her symptoms progressed despite these wound management strategies. Over the following days, she developed a geometric-patterned erythematous plaque with full-thickness epidermal necrosis, characterized by white–gray discoloration and extensive sheet-like desquamation of the RUE (Fig. 1, B). She was subsequently transferred to our institution for higher-level care in a regional burn center. On admission, her exam revealed worsening desquamation with exposed, beefy red underlying skin, suggestive of significant epidermal loss and ongoing inflammatory response (Fig. 1, C).

Fig. 1.

Mirvetuximab Soravatansine extravasation injury in a patient with recurrent ovarian cancer (A) 1 day post-infusion, (B) 6 days post-infusion, (C) 8 days post-infusion, (D) 11 days post-infusion, (E) 37 days post infusion.

Plastic surgery was consulted, and surgical debridement or skin grafting was not deemed necessary. The patient was monitored closely with neurovascular checks every four hours. In collaboration with dermatology and wound care specialists, the frequency of dressing changes was reduced from three times per day to once daily as frequent manipulation was thought to exacerbate skin irritation and bleeding (Fig. 1, D). Topical management included petroleum jelly and silver sulfadiazine cream applied directly to the affected area, which was then covered with a borderless absorbent foam dressing (non-adhesive side on the skin) and loosely secured with gauze. A one-time dose of 20,000 international units of vitamin D3 was given to support wound healing. Infectious disease consultants identified an area under the right axilla concerning for cellulitis or lymphangitic spread and recommended continuing IV cefazolin.

She was discharged after an 18-day hospitalization with gynecologic oncology, dermatology, and physical therapy outpatient follow up. She was instructed to complete a 7-day course of oral cephalexin.

At her two-week follow-up, the patient’s physical exam demonstrated continued improvement (Fig. 1, E). She remained afebrile and without leukocytosis. A central venous access device (VAD) was subsequently placed, and she completed cycle 3 of MIRV without complication.

3. Discussion

This case describes total epidermal necrosis following MIRV administration for platinum resistant recurrent primary peritoneal carcinoma. Despite recognition and conservative management, she experienced significant cutaneous toxicity requiring multidisciplinary care and prolonged hospitalization.

Extravasation events are rare and likely underreported due to the lack of a centralized reporting system. They result from vein wall injury either during IV placement, patient movement, or accidental tugging. Chemotherapeutic agents are classified as neutrals, irritants, or vesicants based on their potential to cause injury during extravasation. While neutrals cause minimal harm, irritants may result in pain and inflammation, and vesicants can lead to blistering and necrosis. Early signs such as swelling and erythema may be subtle or delayed (presenting days after IV infusion), as in this case. Patient-specific risk factors include fragile veins, obesity, multiple prior venipunctures, use of rigid devices (e.g., butterfly needles), and prior exposure to low-pH agents. During infusions, warning signs such as slowed flow, pump alarms, or resistance at the IV site should prompt immediate evaluation.

Many institutions have established protocols in place for suspected extravasation injury. Cytotoxic chemotherapies, specifically, are guided by standardized protocols. Conservative management includes immediate cessation of the infusion, aspiration of the drug with a 1–3 mL syringe through the existing IV site, limb elevation, inspection for signs of tissue damage (e.g., discoloration, swelling, tenderness), application of warm or cold compresses, close clinical monitoring, and thorough documentation (Kim et al., 2020, Wengström and Margulies, 2008, Albert-Marí et al., 2021). For known vesicants, antidotes may be administered as applicable. In severe cases, including compartment syndrome, involvement of joints or neurovascular structures, or failed wound healing, surgical intervention such as fasciotomy, debridement, or skin grafting may be required. A summary of general management steps for extravasations injury is illustrated in Fig. 2.

Fig. 2.

In this case, aspiration was not performed upon recognition of MIRV extravasation. Aspiration is a critical step in limiting tissue damage, as it removes residual drug before further infiltration occurs (Goolsby and Lombardo, 2006). Importantly, aspiration should be done only through the existing catheter site—multiple punctures should be avoided, as they compromise skin integrity and elevate infection risk. Additional potential standard of care management includes photographic documentation of the infusion site’s appearance and recording the volume of drug remaining in the infusion bag at the time of the event. These details help estimate the amount of extravasated vesicant and inform prognosis and follow-up care.

Extravasation injuries are most often recognized during or immediately after infusion; however, delayed presentations—ranging from several days to weeks—have also been described, as in this case. Late manifestations are typically more severe and may include inflammation, discoloration, or blistering (Pérez Fidalgo et al., 2012). Because delayed onset is possible, patients should receive education on the signs and symptoms of extravasation and be instructed to report any changes promptly. Although extravasation events are frequently underreported, the incidence of chemotherapy-related extravasation is estimated to range from < 1 % to 4.5 % (Amit Bahl et al., 2023). The proportion of cases presenting in a delayed fashion is not well characterized in the literature. Nonetheless, most patients demonstrate some degree of infiltration during infusion that prompts the healthcare team to halt administration, as occurred in this case. Timely recognition and intervention remain critical to minimizing tissue injury and optimizing outcomes (Kim et al., 2020). While the initial concern was for acute infection; the patient’s down trending leukocytosis combined with worsening pain despite antibiotic therapy suggested deeper soft tissue damage. A high index of suspicion is essential in such scenarios. Adjunctive measures like high-dose vitamin D have been shown to enhance wound healing through modulating the inflammatory response, reducing extracellular matrix deposition, and delaying epithelial-mesenchymal transition (Oda et al., 2018). Similarly, reducing the frequency of dressing changes contributes to both pain relief and improved wound healing. The maintenance of a moist wound environment with decreased dressing changes facilitates epithelial migration and re-epithelialization (Lagziel et al., 2021, Hill et al., 2025, Romanowski et al., 2020).

As the clinical use of ADCs—including MIRV—continues to expand, reports of severe extravasation injuries remain rare. Similar reports have been described with other ADCs. These include trastuzumab emtansine, enfortumab vedotin, brentuximab vedotin, tisotumab vedotin, and the investigational anti-KAAG1 ADC ADCT-901 (Rivasi et al., 2024, Sallevelt et al., 2020, Grant et al., 2023, Trisha Kaundinya and Zheng, 2024, Shafaee et al., 2017, Son et al., 2024). In these cases, events were reported across a wide range of treatment cycles—from early to late in therapy—including ADCT-901 (cycle 1, day 5), trastuzumab-emtansine (cycles 2 and 8, symptoms developing within hours to two days), enfortumab vedotin (cycles 2 and 4, symptoms on day 8), tisotumab vedotin (cycle 2, day 5), and brentuximab vedotin (cycle 9, day 3). These reports suggest that extravasation may occur at any treatment stage, and risk does not appear to be cumulative or cycle dependent. Notably, none of the previously reported extravasation injury ADCs target folate FRα, yet several share cytotoxic payloads with mechanisms similar to MIRV. Trastuzumab emtansine carries a maytansinoid payload (DM1), while enfortumab vedotin and brentuximab vedotin utilize monomethyl auristatin E. Both DM1 and MIRV’s DM4 are maytansinoids that bind tubulin and inhibit microtubule polymerization. This raises important questions about ADC toxicity. Despite their tumor-specific nature, ADCs may still cause local tissue injury if extravasated. In MIRV’s case, although FRα is not expressed in skin or soft tissue, significant injury occurred. MIRV incorporates a glutathione-cleavable disulfide linker, which exploits the elevated intracellular glutathione levels in tumor cells and ensures intracellular activation. Upon internalization, the linker is cleaved, releasing DM4, the potent anti-tubulin agent. However, disulfide linkers are less stable than non-cleavable alternatives and may release the payload extracellularly under certain conditions, contributing to off-target toxicity. Additional factors such as immune-mediated inflammation or local tissue susceptibility may also play a role in unintended linker cleavage.

Although MIRV does not carry an FDA boxed warning for vesicant potential, its payload shares mechanistic similarities with vinca alkaloids – a class of well-recognized vesicants. At high concentrations or in extravasation settings, these agents may induce tissue damage similar to established vesicants. Management of vinca alkaloid extravasation typically includes warm compresses and hyaluronidase, which may also be explored as potential interventions for MIRV-related injuries. Whether the toxicity is primarily driven by the payload, the linker, or both, remains uncertain.

Given these risks, proactive strategies should be considered. Central venous access devices (VADs) may offer a safer alternative for administration, as their placement in large, high-flow vessels reduces the likelihood and severity of extravasation. Additionally, central VADs are more stable and less prone to displacement, further minimizing risk. Patient-specific factors that may warrant central venous access include fragile or difficult-to-access peripheral veins due to age, prior venous damage, obesity (particularly BMI > 30), lymphedema, central venous obstruction, or a history of prior extravasation injury. Drug-related considerations include agents with vesicant or high cytotoxic potential, prolonged infusions exceeding 60 min, or large-volume administration (Pérez Fidalgo et al., 2012, Coyle et al., 2015). Improved adherence to extravasation management protocols and thorough documentation are critical. As ADCs become more widely adopted, establishing anticipatory strategies for their safe administration and increased recognition of these rare side effects will be essential.

4. Consent statement

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

CRediT authorship contribution statement

Oriana Krivenko: Writing – review & editing, Writing – original draft, Visualization, Resources, Investigation. Jenna Scott Powers: Writing – review & editing, Resources. Connor C. Wang: Writing – review & editing, Supervision, Project administration. Olivia W. Foley: Writing – review & editing, Supervision, Project administration. Emily Hinchcliff: Writing – review & editing, Visualization, Supervision, Project administration, Conceptualization. Emma Barber: Writing – review & editing, Project administration, Conceptualization. Dario Roque: Writing – review & editing, Supervision, Conceptualization.

Conflict of Interest

Emily Hinchcliff disclosed that she serves on the speakers bureau for AbbVie. Emma Barber disclosed that she serves on the scientific advisory board for Merck and is a consultant for GSK. Dario Roque disclosed that he serves on the speakers bureau for Merck and GSK, and on the advisory boards for Merck, GSK, and AbbVie.