Table 1.
Univariate and multivariate analyses by Cox Regression on PFS by investigator assessment.a
| Baseline variable | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | |
| Treatment (lenalidomide versus IC) | 0·65 (0·48–0·87) | 0·005 | 0·42 (0·28–0·62) | <0·001 |
| MIPI‐based characteristics | ||||
| MIPI score at diagnosis (high versus low/intermediate)b | 1·57 (1·12–2·20) | 0·009 | — | — |
| MIPI score at baseline (high versus low/intermediate)b | 2·11 (1·57–2·83) | <0·001 | 1·51 (1·00–2·27) | 0·052 |
| Age, years (≥65 vs. <65) | 1·02 (0·75–1·38) | 0·919 | — | — |
| ECOG PS (2 vs. 0–1) | 1·46 (0·99–2·16) | 0·053 | — | — |
| LDH (high versus low/normal)c | 2·00 (1·49–2·67) | <0·001 | 2·02 (1·35–3·01) | <0·001 |
| WBC (≥10 × 109/l vs. <10 × 109/l) | 1·55 (1·08–2·21) | 0·017 | — | — |
| Other patient characteristics | ||||
| Sex (female versus male) | 0·86 (0·62–1·18) | 0·348 | — | — |
| MCL stage at diagnosis (III/IV versus I/II) | 0·81 (0·46–1·42) | 0·461 | — | — |
| Tumour burden (low versus high)d | 0·81 (0·60–1·08) | 0·155 | — | — |
| Bulky disease (yes versus no)e | 1·40 (0·98–2·01) | 0·063 | 1·57 (1·01–2·43) | 0·045 |
| Bone marrow assessment (negative versus indeterminate/positive)f | 0·72 (0·44–1·20) | 0·206 | — | — |
| Renal function (normal versus moderate/severe insufficiency)g | 0·60 (0·43–0·84) | 0·003 | — | — |
| Prior treatment history | ||||
| Time from MCL diagnosis to first dose (≥3 versus <3 years) | 0·85 (0·64–1·14) | 0·280 | — | — |
| Number of prior systemic antilymphoma therapies (≥3 versus <3) | 1·51 (1·11–2·06) | 0·009 | 1·75 (1·19–2·58) | 0·005 |
| Disease status to last prior therapy (relapsedh versus refractory) | 0·77 (0·58–1·03) | 0·075 | — | — |
| Time from last prior therapy to first dose (≥6 vs. <6 months) | 0·74 (0·55–0·98) | 0·034 | 0·68 (0·47–0·97) | 0·032 |
| Time since last rituximab to first dose (≥230 vs. <230 days) | 0·79 (0·59–1·07) | 0·127 | — | — |
| Prior HDT (yes versus no)i | 0·98 (0·68–1·42) | 0·930 | — | — |
| Prior SCT (yes versus no) | 0·96 (0·66–1·39) | 0·837 | — | — |
95% CI, 95% confidence interval; CR, complete response; CrCl, creatinine clearance; ECOG PS, Eastern Cooperative Oncology Group performance status; HDT, high‐dose therapy; HR, hazard ratio; LDH, lactate dehydrogenase; MCL, mantle cell lymphoma; MIPI, MCL International Prognostic Index; PFS, progression‐free survival; SCT, stem cell transplantation; WBC, white blood cell count.
Variables with P value <0·20 in the univariate analysis were selected for multivariate analysis. Final variables were selected using a stepwise selection method with entry level = 0·20 and stay level = 0·15. Multivariate survival analysis using Cox's regression model was estimated using 162 patients.
MIPI score = 0·03535 * age + 0·6978 * (if ECOG PS >1) + 1·367 * log10 (LDH/upper limit of normal) + 0·9393 * log10 (WBC per 10−6/l).
High LDH was >3·4 μkat/l for patients aged ≤60 years and >3·5 μkat/l for those aged >60 years; low LDH was <1·8 μkat/l; normal was defined per local laboratory criteria.
High tumour burden was defined by at least one lesion ≥5 cm in diameter or three lesions ≥3 cm in diameter by central radiology review.
Bulky disease was defined by at least one lesion ≥7 cm in the longest diameter by central radiology review.
For estimation of bone marrow involvement by local pathologist, negative was defined as having no aggregates or only a few well‐circumscribed lymphoid aggregates, indeterminate bone marrow was defined as having an increased number/size of lymphoid aggregates without overt malignancy, and positive was defined as an unequivocal malignancy.
Normal renal function was defined as CrCl of ≥60 ml/min; moderate insufficiency had CrCl ≥30 to <60 ml/min but not requiring dialysis; severe insufficiency had CrCl <30 ml/min. 2 patients had severe insufficiency in this study.
Relapse included patients with best response to last treatment of CR, unconfirmed CR, or partial response.
HDT was defined as SCT, hyper‐CVAD (hyper fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone plus methotrexate and cytarabine), or R‐hyper‐CVAD (rituximab + Hyper CVAD).