RISK STRATIFICATION AND PROGNOSIS

Since treatment may differ depending on the stage of the disease, in-depth evaluation should occur at the initial staging.1,2 The MIPI score is based on several independent prognostic factors at the time of diagnosis, including: age, ECOG performance status, LDH, and white blood cell count – in one study, a high-risk MPI score was associated with poor survival.1,2

For treatment purposes, MCL has been categorized into two major subgroups, these subgroups are now included in the WHO 2016 update of lymphoid malignancies.3

The subgroups of MCL are distinct in clinical presentation and molecular features.3

  • Conventional MCL3
    • This is a bulky nodal/extranodal variant with an aggressive disease course
  • Smouldering nodal/extra-nodal and leukemic non-nodal MCL3
    • This is seen in 10% to 20% of MCL patients
    • In most cases, it is generally associated with indolent disease course and superior outcome

MIPI RISK STRATIFICATION

zoom

TABLE 2. SIMPLIFIED MIPI PROGNOSTIC INDEX2

Points (from 0–3/per Prognostic Factor) Age (years) ECOG Performance Status LDH (ULN) WBC (109/L)
0 <50 0-1 <0.67 <6.70
1 50–59 0.67–0.99 6.7–9.99
2 60–69 2-4 1.00–1.49 10.00–14.99
3 ≥70 ≥1.50 ≥15.00

Adapted from Leukemia & Lymphoma Society.
ECOG=Eastern Cooperative Oncology Group; LDH=lactate dehydrogenase; ULN=upper limit of normal; WBC=white blood cell.

For each prognostic factor, 0–3 points were given to each patient to a maximum of 11.2

  • Patients with 0–3 points in total were classified as low-risk, patients with 4−5 points as intermediate-risk, and patients with 6–11 points as high-risk2
  • ECOG performance status was weighted with 2 points if patients were unable to work or bedridden (ECOG 2–4)4
  • LDH was weighted according to the ratio to the ULN4
    • For example an ULN of 240 U/L, the limits were 180, 240 and 360 U/L for low-, intermediate- and high-risk groups, respectively

This risk assessment can help plan the next steps for treatment of MCL by dividing it into:1,3

  • Indolent disease – watch and wait

or

  • Aggressive disease – active treatment

or

  • Relapsed/refractory disease – active treatment

SOME CLINICAL AND MOLECULAR CHARACTERISTICS, SUCH AS BLASTOID MORPHOLOGY, HIGH-RISK MIPI SCORE AND HIGH KI-67, HAVE BEEN SHOWN TO HELP PREDICT OUTCOMES IN MCL PATIENTS1

chart 1

Adapted from Eskelund et al., 2017.

chart 2

Adapted from Hoster et al., 2016.

chart 3

Adapted from Hoster et al., 2016.

chart 4

Adapted from Eskelund et al., 2017.

THE MCL DIAGNOSTIC PROCESS

Staging and prognostic indexes, such as the MIPI, can help inform appropriate treatment strategies based on individual patient risk factors.2

Given the aggressive nature of MCL, approximately 70–80% of patients are symptomatic and require treatment immediately following diagnosis and staging (Table 3).2,3

zoom

TABLE 3. MCL MANAGEMENT BASED ON CLASSIFICATION

Asymptomatic/indolent patients: 1–3 Symptomatic/aggressive disease 1,2
This can be safely watched initially without any compromise to long-term outcome.
  • Low proliferation index
  • Good performance status
  • Non-bulky disease
  • Low MIPI score
  • Normal LDH levels
  • Low Ki-67%
  • Non-aggressive cytomorphology
 Treatment choice is based on the patient’s age and fitness.
  • Younger/fit patients are offered intensive combination regimens, usually followed by autologous stem cell rescue
  • Older individuals are frequently not suitable for a dose-intensive style of therapy and chemo-immunotherapy currently remains the backbone of treatment