How do you count lines of therapy in lymphoma?

Counting Lines of Therapy in Lymphoma

In lymphoma, a line of therapy is defined by a specific treatment regimen or protocol given for a specific intent, and continues until treatment completion, progression, or intolerable toxicity necessitates a change to a different regimen.

Definition and Basic Principles

• A line of therapy refers to a specific treatment regimen (single agent or combination) administered with a specific intent (induction, consolidation, maintenance)
• Each distinct regimen counts as one line of therapy, regardless of the number of cycles administered

When a New Line of Therapy Begins

A new line of therapy is counted when:

1. Disease progression occurs during treatment, requiring a switch to a different regimen
2. Treatment is changed due to unacceptable toxicity
3. A planned change to a completely different regimen occurs (not just dose modifications)
4. Relapse occurs after a period of remission, requiring reinitiation of treatment

Common Treatment Scenarios in Lymphoma

First-Line Therapy

• Standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) 1
• For Hodgkin lymphoma, standard first-line therapy is ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) or BEACOPPescalated (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) 1

Second-Line Therapy

• For relapsed/refractory DLBCL, salvage regimens like R-DHAP, R-ESHAP, R-ICE, etc., followed by high-dose therapy with stem cell support in responsive patients 1
• For relapsed Hodgkin lymphoma, salvage regimens such as DHAP or IGEV followed by high-dose chemotherapy and autologous stem cell transplantation 1

Special Considerations

Maintenance Therapy

• Maintenance therapy (such as rituximab maintenance after initial immunochemotherapy in follicular lymphoma) is considered part of the same line of therapy as the induction regimen that preceded it 2

Consolidation Therapy

• Consolidation therapy (such as radiation therapy after chemotherapy or autologous stem cell transplantation after salvage therapy) is considered part of the same line of therapy

Dose Modifications

• Dose modifications or delays within the same regimen do not constitute a new line of therapy
• Switching from one agent to another within the same regimen due to toxicity (e.g., switching from doxorubicin to etoposide in R-CHOP) does not constitute a new line of therapy

Clinical Examples

1. Example 1: A patient receives 6 cycles of R-CHOP for DLBCL and achieves complete remission. Six months later, the disease relapses and the patient receives R-ICE followed by autologous stem cell transplantation.

   • First line: R-CHOP
   • Second line: R-ICE + autologous stem cell transplantation

2. Example 2: A patient with Hodgkin lymphoma receives 2 cycles of ABVD but develops pulmonary toxicity from bleomycin, so treatment is changed to AVD (adriamycin, vinblastine, dacarbazine) for 4 more cycles.

   • This is still considered first-line therapy as it's a modification of the same regimen

3. Example 3: A patient with follicular lymphoma receives R-CHOP followed by 2 years of rituximab maintenance. After completion, the disease relapses and the patient receives bendamustine plus rituximab.

   • First line: R-CHOP + rituximab maintenance
   • Second line: Bendamustine + rituximab

Common Pitfalls to Avoid

• Pitfall 1: Counting planned sequential regimens as separate lines of therapy

  • Example: In advanced Hodgkin lymphoma, 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD is considered one line of therapy if this was the planned approach 1

• Pitfall 2: Counting radiation therapy after chemotherapy as a separate line

  • Example: ABVD followed by involved-field radiation therapy for early-stage Hodgkin lymphoma is one line of therapy 1

• Pitfall 3: Counting dose modifications or growth factor support as new lines of therapy

  • Example: Adding G-CSF support to prevent neutropenia during CHOP therapy does not constitute a new line 1

Accurate counting of lines of therapy is critical for clinical decision-making, clinical trial eligibility, and insurance coverage determinations in lymphoma management.