EHA 2019 | Results of the phase II LYMA-101 trial

On 14 June 2019, at the 24^th European Hematology Association Congress in Amsterdam, Steven Le Gouill, from Chu de Nantes, Nantes, FR, presented results of the LYMA-101 phase II trial. This study found that obinutuzumab plus DHAP (O-DHAP) followed by autologous stem cell transplantation (ASCT) plus obinutuzumab maintenance, provided a high minimal residual disease (MRD) response rate in untreated patients with mantle cell lymphoma (MCL).

The primary objective of the study was the MRD negativity rate after four cycles of O-DHAP and was assessed by IGH clonospecific testing or bcl1-JH PCR quantification. Secondary objectives included overall response rate (ORR), complete response (CR), progression-free survival (PFS), overall survival (OS), incidence of stem cell collection failure, duration of MRD response and tolerability.

Patient sets

• Included set (n = 86), all patients who signed informed consent
• Safety set (n = 85), all patients who had at least one dose of obinutuzumab
• Efficacy set (n = 73), all patients who had at least one dose of obinutuzumab and were MRD informative in bone marrow at baseline for a clonal IG or BCL1-IGH molecular marker

Patient characteristics (included set, n=86)

• MCL Ann Arbor stage II-IV, 97.7% were stage III or above in the included set, in comparison to 100% in the efficacy set
• Phenotypic expression of CD5, CD20 and cyclin D1 and/or translocation (11;14)
• Eligible for autologous stem cell transplant
• No progressive multifocal leukoencephalopathy (PML)
• Treatment naïve adults <66 years of age, median age 63
• ECOG performance status of 0–2 , 63% of patients were ECOG 0 in the efficacy set, in comparison to 64% in the included set
• Blastoid morphology in the included set, 17.4%, in comparison to 16.4% in the efficacy set
• Median percent Ki67 positive in the included set 30% in both groups

Methods

• Induction consisting of four cycles of O-DHAP
• Consolidation with ASCT, followed by obinutuzumab maintenance for three years
• After this, obinutuzumab on-demand for MRD positive patients

Key findings

• After the end of induction, qPCR (quantitative polymerase chain reaction) showed that 75% of patients were MRD negative in bone marrow, while the ddPCR (droplet digital polymerase chain reaction) method showed it to be 85% of patients
• The main reasons for stopping treatment were due to adverse events (AEs)

Table 1. Details on discontinuations in the safety set, n = 85

 Discontinuations

Safety set (n = 85)

All discontinuations

25

AEs

13

Progression

3

Secondary malignancy (e.g. squamous cell carcinoma tonsil, MDS)

3

Physician decision

2

Death

2

Major protocol violation

1

Voluntary discontinuation/consent withdrawal

1

Table 2. Timings of when patients discontinued treatment in the safety set, n = 85

Period

Safety set (n = 85)

Before treatment

1

Before ASCT

4

Before maintenance

11

During maintenance

9

• Main toxicities in the safety set during induction included thrombocytopenia, neutropenia, anemia, leukopenia, lymphopenia and febrile neutropenia
• One-year PFS was 93.4%, and one-year OS was 96%

Conclusion

• The trial successfully reached its primary end point
• No major toxicities were reported, and O-DHAP has high efficacy as an induction regimen
• One-year OS and PFS are encouraging, however longer follow-up is necessary to evaluate patient outcomes