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N. Shah
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-003 - Novel Fusion Protein ALK-MPRIP Exhibits ALK Activation and Sensitivity to Crizotinib (ID 1294)
09:30 - 09:30 | Author(s): N. Shah
- Abstract
Background:
Rearrangement of the ALK gene is an important therapeutic pathway in NSCLC. EML4 is the partner gene in the vast majority of ALK driven cancers, with other variants rarely reported. The clinical characteristics and sensitivity to ALK targeted agents in patients with non-EML4 variants are unknown.
Methods:
We report a patient case with a novel fusion of ALK-MPRIP (myosin phosphatase-Rho-interacting protein gene). A 49-year-old Caucasian female with less than 10 pack-year smoking history presented with chest pain and dyspnea on exertion. Chest x-ray showed mild CHF. An echocardiogram demonstrated a large pericardial effusion with tamponade physiology. She underwent a pericardial window with cytology of the pericardial fluid demonstrating adenocarcinoma, positive for TTF1 and napsin, consistent with lung primary. CT imaging revealed cervical and mediastinal adenopathy, bilateral pleural effusions, small lung nodules. She was staged as TxN3M1a. She was negative for EGFR and ALK by FISH. Tissue was sent for next generation sequencing due to her light smoking history, which revealed a never before characterized ALK-MPRIP fusion. As the functional significance of this alteration was unknown, she continued Carboplatin/Pemetrexed/Bevacizumab therapy for 4 cycles followed by 6 cycles of maintenance Pemetrexed/Bevacizumab before documented progression. She was subsequently started on Crizotinib.
Results:
Two months after starting Crizotinib, CT scans demonstrated decreased lung nodules, lymphadenopathy and improved interstitial thickening. After 5 months of treatment CT scans demonstrated new ground glass opacities with increasing bilateral interlobular septal thickening concerning for either Crizotinib-induced lung toxicity or lymphangitic carcinomatosis. Bronchoscopy with transbronchial biopsy demonstrated lymphangitic spread suggestive of progression on Crizotinib within 6 months of therapy. The average PFS of Crizotinib treated EML4-ALK translocated patients is 7.7 months.Figure 1Figure 2
Conclusion:
ALK-MPRIP is a novel fusion gene causing ALK activation. Our patient responded to Crizotinib but had a shorter than average PFS compared to EML4-ALK mutated patients.
